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      A global point prevalence survey of antimicrobial use in neonatal intensive care units: The no-more-antibiotics and resistance (NO-MAS-R) study

      research-article
      , PharmD a , , PharmD b , , BA c , , BPharm d , , MD e , , MD f , , MD g , , MD h , , MBChB i , , MD j , , MBBS k , , MD l , , MD m , , MD n , , MD o , , MD p , , MD q , , PhD r , , MD s , , MD t , , MD u , , PharmD v , , MD w , , PharmD x , , MBBS y , , MD z , , MD aa , , MD ab , , MD ac , , MD ad , , MD ae , , MD af , , PharmD ag , , MD ah , , MD ai , , MD aj , , PharmD ak , , MD al , , MD am , , MD an , , MD ao , , MD ap , , MD aq , , MD ar , , MD as , , MD at , , MD au , , PharmD av , , MD aw , , MD ax , , MD ay , , PharmD az , , MD ba , , MD bb , , MD bc , , MD bd , , BPharm be , , MD bf , , MD bg , , FRCPCH bh , , MD bi , , MD bj , , MD bk , , MD bl , , MD bm , , MD bn , , MD bo , , MD bp , , MD bq , , MD br , , MD bs , , MD bt , , MD bu , , MD bv , , MD bw , , MD c , bx , c , bx , * , for the Global NEO-ASP Study Group
      EClinicalMedicine
      Elsevier
      Global point prevalence study, Neonatal infection, Neonatal antimicrobial stewardship, Antibiotics, Antifungal

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          Abstract

          Background

          Global assessment of antimicrobial agents prescribed to infants in the neonatal intensive care unit (NICU) may inform antimicrobial stewardship efforts.

          Methods

          We conducted a one-day global point prevalence study of all antimicrobials provided to NICU infants. Demographic, clinical, and microbiologic data were obtained including NICU level, census, birth weight, gestational/chronologic age, diagnoses, antimicrobial therapy (reason for use; length of therapy), antimicrobial stewardship program (ASP), and 30-day in-hospital mortality.

          Findings

          On July 1, 2019, 26% of infants (580/2,265; range, 0–100%; median gestational age, 33 weeks; median birth weight, 1800 g) in 84 NICUs (51, high-income; 33, low-to-middle income) from 29 countries (14, high-income; 15, low-to-middle income) in five continents received ≥1 antimicrobial agent (92%, antibacterial; 19%, antifungal; 4%, antiviral). The most common reasons for antibiotic therapy were “rule-out” sepsis (32%) and “culture-negative” sepsis (16%) with ampicillin (40%), gentamicin (35%), amikacin (19%), vancomycin (15%), and meropenem (9%) used most frequently. For definitive treatment of presumed/confirmed infection, vancomycin (26%), amikacin (20%), and meropenem (16%) were the most prescribed agents. Length of therapy for culture-positive and “culture-negative” infections was 12 days (median; IQR, 8–14) and 7 days (median; IQR, 5–10), respectively. Mortality was 6% (42%, infection-related). An NICU ASP was associated with lower rate of antibiotic utilization ( p = 0·02).

          Interpretation

          Global NICU antibiotic use was frequent and prolonged regardless of culture results. NICU-specific ASPs were associated with lower antibiotic utilization rates, suggesting the need for their implementation worldwide.

          Funding

          Merck & Co.; The Ohio State University College of Medicine Barnes Medical Student Research Scholarship

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          Most cited references66

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          Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support.

          Research electronic data capture (REDCap) is a novel workflow methodology and software solution designed for rapid development and deployment of electronic data capture tools to support clinical and translational research. We present: (1) a brief description of the REDCap metadata-driven software toolset; (2) detail concerning the capture and use of study-related metadata from scientific research teams; (3) measures of impact for REDCap; (4) details concerning a consortium network of domestic and international institutions collaborating on the project; and (5) strengths and limitations of the REDCap system. REDCap is currently supporting 286 translational research projects in a growing collaborative network including 27 active partner institutions.
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            The REDCap consortium: Building an international community of software platform partners

            The Research Electronic Data Capture (REDCap) data management platform was developed in 2004 to address an institutional need at Vanderbilt University, then shared with a limited number of adopting sites beginning in 2006. Given bi-directional benefit in early sharing experiments, we created a broader consortium sharing and support model for any academic, non-profit, or government partner wishing to adopt the software. Our sharing framework and consortium-based support model have evolved over time along with the size of the consortium (currently more than 3200 REDCap partners across 128 countries). While the "REDCap Consortium" model represents only one example of how to build and disseminate a software platform, lessons learned from our approach may assist other research institutions seeking to build and disseminate innovative technologies.
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              Neonatal sepsis.

              Neonatal sepsis is the cause of substantial morbidity and mortality. Precise estimates of neonatal sepsis burden vary by setting. Differing estimates of disease burden have been reported from high-income countries compared with reports from low-income and middle-income countries. The clinical manifestations range from subclinical infection to severe manifestations of focal or systemic disease. The source of the pathogen might be attributed to an in-utero infection, acquisition from maternal flora, or postnatal acquisition from the hospital or community. The timing of exposure, inoculum size, immune status of the infant, and virulence of the causative agent influence the clinical expression of neonatal sepsis. Immunological immaturity of the neonate might result in an impaired response to infectious agents. This is especially evident in premature infants whose prolonged stays in hospital and need for invasive procedures place them at increased risk for hospital-acquired infections. Clinically, there is often little difference between sepsis that is caused by an identified pathogen and sepsis that is caused by an unknown pathogen. Culture-independent diagnostics, the use of sepsis prediction scores, judicious antimicrobial use, and the development of preventive measures including maternal vaccines are ongoing efforts designed to reduce the burden of neonatal sepsis.
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                Author and article information

                Contributors
                Journal
                EClinicalMedicine
                EClinicalMedicine
                EClinicalMedicine
                Elsevier
                2589-5370
                29 January 2021
                February 2021
                29 January 2021
                : 32
                : 100727
                Affiliations
                [a ]Department of Pharmacy, Nationwide Children's Hospital, Columbus, OH, USA
                [b ]Department of Pharmacy, The Ohio State University Wexner Medical Center, The Ohio State University College of Pharmacy, Columbus, OH, USA
                [c ]The Ohio State University College of Medicine, Columbus, OH, USA
                [d ]Chris Hani Baragwanath Hospital, Johannesburg, South Africa
                [e ]Health Equity International, Fond- des- Blancs, Haiti
                [f ]Department of Neonatology, Pontificia Universidad Catolica, Santiago, Chile
                [g ]Division of Neonatology and NICU, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
                [h ]Department of Neonatology, Wuhan Children's Hospital Wuhan Maternal and Child Healthcare Hospital Tongji Medical College Huazhong University of Science & Technology, Wuhan, China
                [i ]Department of Pediatric Surgery, Lagos University Teaching Hospital, Lagos, Nigeria
                [j ]University of Virginia School of Medicine, Charlottesville, VA, USA
                [k ]Division of Paediatric Surgery, National Hospital, Abuja, Nigeria
                [l ]Pediatric Infectious Diseases Unit and Faculty of Health Sciences, Ben Gurion University of the Negev, Soroka University Medical Center, Beer Sheva, Israel
                [m ]Department of Pediatrics, Newborn Section, Universidade Federal do Rio Grande do Sul. Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil
                [n ]Department of Neonatology, Bambino Gesù Children's Hospital, Rome, Italy
                [o ]Clinica del Prado and Clinica El Rosario, Medellin, Colombia
                [p ]Division of Neonatology, Hospital Materno Infantil Gregorio Marañon University Hospital, Madrid, Spain
                [q ]Division of Pediatric Infectious Diseases, Puerta del Mar University Hospital, Cadiz, Spain
                [r ]Department of Medical Microbiology, University of Ghana Medical School, Accra, Ghana
                [s ]Division of Pediatric Infectious Diseases, Children's Hospital, Helsinki University Hospital, Helsinki, Finland
                [t ]Division of Neonatology, Treviso Hospital, Treviso, Italy
                [u ]Clinica Soma, Procaren NICU, CES University, Medellin, Colombia
                [v ]Department of Pharmacy, St. Vincent Women's Hospital, Indianapolis, IN, United States
                [w ]Department of Neonatology, Hospital Nacional Cayetano Heredia, Lima, Peru
                [x ]Department of Pharmacy, Arnold Palmer Hospital for Children, Orlando, FL, USA
                [y ]University of Guyana, School of Medicine, Georgetown, Guyana
                [z ]Division of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital, Utrecht, Netherlands
                [aa ]Coordinator of Neonatology Fellow Program, Head of Neonatal Intensive Care, University of Antioquia, Hospital San Vicente Fundacion, Medellin, Colombia
                [ab ]Department of Neonatology, Instituto de Maternidad Ntra. Sra. de las Mercedes, San Miguel de Tucumán, Argentina
                [ac ]Division of Neonatology, Hospital General Dr. Ignacio Morones Prieto, San Luis Potosi, Mexico
                [ad ]Division of Neonatology and NICU, G. Salesi Children's Hospital, Ancona, Italy
                [ae ]Division of Neonatology and Pediatric Infectious Diseases, Hospital Barros Luco Trudeau, Santiago, Chile
                [af ]Division of Neonatology and Neonatal Research Group, La Fe University and Polytechnic Hospital, Valencia, Spain
                [ag ]Department of Pharmacy, UCSF Benioff Children's Hospital, San Francisco, CA, USA
                [ah ]Sub-Department of Pediatric Surgery, University of Nigeria Teaching Hospital, Enugu, Nigeria
                [ai ]Division of Neonatology, Hospital 12 de Octubre, Madrid, Spain
                [aj ]Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
                [ak ]Department of Pharmacy, University of Illinois Hospital & Health Sciences System, Chicago, IL, USA
                [al ]Department of Pediatrics, Kyorin University School of Medicine, Tokyo, Japan
                [am ]Division of Neonatology, Hospital General San Francisco, Quito, Ecuador
                [an ]Division of Neonatology and NICU, AOU Policlinico G Rodolico, Catania, Italy
                [ao ]Clínica Universitaria Bolivariana/Universidad Pontificia Bolivariana, Medellín, Colombia
                [ap ]Infectious Diseases Unit, 3rd Department of Pediatrics, Faculty of Medicine, Aristotle University School of Health Sciences, Thessaloniki, Greece
                [aq ]Division of Pediatric Infectious Diseases, Hospital Nacional de Niños, San Jose, Costa Rica
                [ar ]Department of Pediatrics, Nagoya Red Cross Daiichi Hospital, Nagoya, Japan
                [as ]Division of Neonatology, Alberto Sabogal Hospital, Lima, Peru
                [at ]Policlinico Casilino, Rome, Italy
                [au ]Division of Patology and Intensive Neonatal Care, A.O.U. Policlinico di Messina, Messina, Italy
                [av ]Department of Pharmacy, Norton Children's Hospital, Louisville, KY, USA
                [aw ]Department of Pediatrics, Division of Neonatology, University Hospital UT Health San Antonio, San Antonio, TX
                [ax ]Pediatric Infectious Diseases, Hospital General de Medellín, Medellín, Colombia
                [ay ]Department of Women's and Children's Health, Uppsala University, Uppsala University Children's Hospital, Uppsala, Sweden
                [az ]Department of Pharmacy, Parkview Regional Medical Center, Fort Wayne, IN, USA
                [ba ]Iran University of Medical Sciences, Tehran, Iran
                [bb ]Department of Perinatology and Neonatology, Central Military Hospital, Nueva Granada Military University, Bogotá, Colombia
                [bc ]Department of Neonatology, Cliniques Universitaires Saint Luc, Brussels, Belgium
                [bd ]Program Coordinator Pediatric Infectious Diseases Clinica Universiraria Bolivariana, Hospital Pablo Tobon Uribe, Medellin, Colombia
                [be ]Department of Pharmacy, Nelson Mandela Children Hospital, Johannesburg, South Africa
                [bf ]Head of Neonatal Intensive Care, Hospital de los Valles, Quito, Ecuador
                [bg ]Pontificia Universidad Catolica del Ecuador, Hospital Metropolitano Quito, Quito, Ecuador
                [bh ]Child Health Department, Sultan Qaboos University Hospital, Muscat, Oman
                [bi ]Department of Pediatrics, Division of Neonatology, Saint John Regional Hospital, Saint John, Canada
                [bj ]Head of NICU Department, ARNAS Garibaldi, Catania, Italy
                [bk ]Division of Neonatology, American University of Beirut Medical Center, Beirut, Lebanon
                [bl ]Division of Neonatology, Maternal and Children Hospital of Tigre Dr. Florencio Escardó, Tigre, Argentina
                [bm ]Division of Infectious Disease, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Canada
                [bn ]Division of Neonatology and NICU, Careggi Univerisity Hospital, Florence, Italy
                [bo ]G. Fornaroli Hospital, Magenta, Milan, Italy
                [bp ]Ospedale Miulli, Acquaviva, Italy
                [bq ]Research and Development Center for New Medical Frontiers, Department of Advanced Medicine, Division of Neonatal Intensive Care Medicine, Kitasato University School of Medicine, Sagamihara, Japan
                [br ]Division of Pediatric Infectious Diseases, The Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
                [bs ]Division of Pediatrics and Neonatology, Degli Infermi Hospital, Biella, Italy
                [bt ]Hospital del Niño, Panama, Panama
                [bu ]Division of Neonatology, Clínica del Country / Clínica La Colina, Bogotá, Colombia
                [bv ]Hospital San Jose, Bogotá, Colombia
                [bw ]Hospital Universitario de Salamanca, Salamanca, Spain
                [bx ]Department of Pediatrics, Divisions of Neonatology and Pediatric Infectious Diseases, Nationwide Children's Hospital, Center for Perinatal Research, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA
                Author notes
                [* ]Corresponding author at: Divisions of Neonatology and Pediatric Infectious Diseases, Nationwide Children's Hospital - The Ohio State University College of Medicine, Center for Perinatal Research, Abigail Wexner Research Institute at Nationwide Children's Hospital, 700 Children's Drive, RB3, WB5245, Columbus, Ohio 43205-2664, United States. Pablo.Sanchez@ 123456nationwidechildrens.org
                Article
                S2589-5370(21)00007-9 100727
                10.1016/j.eclinm.2021.100727
                7848759
                33554094
                f34a196e-fd0b-4d5d-bf22-a4c3765c4953
                © 2021 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 25 September 2020
                : 4 January 2021
                : 8 January 2021
                Categories
                Research Paper

                global point prevalence study,neonatal infection,neonatal antimicrobial stewardship,antibiotics,antifungal

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