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      Antibiotic Prescriptions and Prophylaxis in Italian Children. Is It Time to Change? Data from the ARPEC Project

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          Abstract

          Background

          Antimicrobials are the most commonly prescribed drugs. Many studies have evaluated antibiotic prescriptions in the paediatric outpatient but few studies describing the real antibiotic consumption in Italian children’s hospitals have been published. Point-prevalence survey (PPS) has been shown to be a simple, feasible and reliable standardized method for antimicrobials surveillance in children and neonates admitted to the hospital. In this paper, we presented data from a PPS on antimicrobial prescriptions carried out in 7 large Italian paediatric institutions.

          Methods

          A 1-day PPS on antibiotic use in hospitalized neonates and children was performed in Italy between October and December 2012 as part of the Antibiotic Resistance and Prescribing in European Children project (ARPEC). Seven institutions in seven Italian cities were involved. The survey included all admitted patients less than 18 years of age present in the ward at 8:00 am on the day of the survey, who had at least one on-going antibiotic prescription. For all patients data about age, weight, underlying disease, antimicrobial agent, dose and indication for treatment were collected.

          Results

          The PPS was performed in 61 wards within 7 Italian institutions. A total of 899 patients were eligible and 349 (38.9%) had an on-going prescription for one or more antibiotics, with variable rates among the hospitals (25.7% - 53.8%). We describe antibiotic prescriptions separately in neonates (<30 days old) and children (> = 30 days to <18 years old). In the neonatal cohort, 62.8% received antibiotics for prophylaxis and only 37.2% on those on antibiotics were treated for infection. Penicillins and aminoglycosides were the most prescribed antibiotic classes. In the paediatric cohort, 64.4% of patients were receiving antibiotics for treatment of infections and 35.5% for prophylaxis. Third generation cephalosporins and penicillin plus inhibitors were the top two antibiotic classes. The main reason for prescribing antibiotic therapy in children was lower respiratory tract infections (LRTI), followed by febrile neutropenia/fever in oncologic patients, while, in neonates, sepsis was the most common indication for treatment. Focusing on prescriptions for LRTI, 43.3% of patients were treated with 3rd generation cephalosporins, followed by macrolides (26.9%), quinolones (16.4%) and carbapenems (14.9%) and 50.1% of LRTI cases were receiving more than one antibiotic. For neutropenic fever/fever in oncologic patients, the preferred antibiotics were penicillins with inhibitors (47.8%), followed by carbapenems (34.8%), aminoglycosides (26.1%) and glycopeptides (26.1%). Overall, the 60.9% of patients were treated with a combination therapy.

          Conclusions

          Our study provides insight on the Italian situation in terms of antibiotic prescriptions in hospitalized neonates and children. An over-use of third generation cephalosporins both for prophylaxis and treatment was the most worrisome finding. A misuse and abuse of carbapenems and quinolones was also noted. Antibiotic stewardship programs should immediately identify feasible targets to monitor and modify the prescription patterns in children’s hospital, also considering the continuous and alarming emergence of MDR bacteria.

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          Most cited references32

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          Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship.

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            The epidemic of antibiotic-resistant infections: a call to action for the medical community from the Infectious Diseases Society of America.

            The ongoing explosion of antibiotic-resistant infections continues to plague global and US health care. Meanwhile, an equally alarming decline has occurred in the research and development of new antibiotics to deal with the threat. In response to this microbial "perfect storm," in 2001, the federal Interagency Task Force on Antimicrobial Resistance released the "Action Plan to Combat Antimicrobial Resistance; Part 1: Domestic" to strengthen the response in the United States. The Infectious Diseases Society of America (IDSA) followed in 2004 with its own report, "Bad Bugs, No Drugs: As Antibiotic Discovery Stagnates, A Public Health Crisis Brews," which proposed incentives to reinvigorate pharmaceutical investment in antibiotic research and development. The IDSA's subsequent lobbying efforts led to the introduction of promising legislation in the 109 th US Congress (January 2005-December 2006). Unfortunately, the legislation was not enacted. During the 110 th Congress, the IDSA has continued to work with congressional leaders on promising legislation to address antibiotic-resistant infection. Nevertheless, despite intensive public relations and lobbying efforts, it remains unclear whether sufficiently robust legislation will be enacted. In the meantime, microbes continue to become more resistant, the antibiotic pipeline continues to diminish, and the majority of the public remains unaware of this critical situation. The result of insufficient federal funding; insufficient surveillance, prevention, and control; insufficient research and development activities; misguided regulation of antibiotics in agriculture and, in particular, for food animals; and insufficient overall coordination of US (and international) efforts could mean a literal return to the preantibiotic era for many types of infections. If we are to address the antimicrobial resistance crisis, a concerted, grassroots effort led by the medical community will be required.
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              Hospital and societal costs of antimicrobial-resistant infections in a Chicago teaching hospital: implications for antibiotic stewardship.

              Organisms resistant to antimicrobials continue to emerge and spread. This study was performed to measure the medical and societal cost attributable to antimicrobial-resistant infection (ARI). A sample of high-risk hospitalized adult patients was selected. Measurements included ARI, total cost, duration of stay, comorbidities, acute pathophysiology, Acute Physiology and Chronic Health Evaluation III score, intensive care unit stay, surgery, health care-acquired infection, and mortality. Hospital services used and outcomes were abstracted from electronic and written medical records. Medical costs were measured from the hospital perspective. A sensitivity analysis including 3 study designs was conducted. Regression was used to adjust for potential confounding in the random sample and in the sample expanded with additional patients with ARI. Propensity scores were used to select matched control subjects for each patient with ARI for a comparison of mean cost for patients with and without ARI. In a sample of 1391 patients, 188 (13.5%) had ARI. The medical costs attributable to ARI ranged from $18,588 to $29,069 per patient in the sensitivity analysis. Excess duration of hospital stay was 6.4-12.7 days, and attributable mortality was 6.5%. The societal costs were $10.7-$15.0 million. Using the lowest estimates from the sensitivity analysis resulted in a total cost of $13.35 million in 2008 dollars in this patient cohort. The attributable medical and societal costs of ARI are considerable. Data from this analysis could form the basis for a more comprehensive evaluation of the cost of resistance and the potential economic benefits of prevention programs.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                16 May 2016
                2016
                : 11
                : 5
                : e0154662
                Affiliations
                [1 ]Immunology and Infectious Diseases Unit, University Hospital Pediatric Department, Bambino Gesù Children's Hospital, Rome, Italy
                [2 ]Division of Pediatric Infectious Diseases, Department for Woman and Child Health, University of Padua, Padua, Italy
                [3 ]Paediatric Infectious Diseases Unit, Department of Paediatric Medicine, Anna Meyer Children's University Hospital, Florence, Italy
                [4 ]Department of Translational Medical Sciences—Section of Pediatrics, University of Naples Federico II, Naples, Italy
                [5 ]Acute Care and Emergency Department, G. Gaslini Children's Hospital, Genoa, Italy
                [6 ]Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
                [7 ]Paediatric Unit, Versilia Hospital, Lido di Camaiore, Italy
                [8 ]Infection and Immunity, Division of Clinical Sciences, St. Georges University of London, London, United Kingdom
                [9 ]Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
                [10 ]Pediatric Unit, San Martino Hospital, Belluno, Italy
                Azienda ospedaliero-universitaria di Perugia, ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MS AV HG GN. Performed the experiments: PD AG LG SE MR CT CC CG. Analyzed the data: MDL DD CM RL. Wrote the paper: MDL DD GN. Revised the manuscript: PD SE LG ALV CM MS AV.

                Author information
                http://orcid.org/0000-0001-7549-3514
                Article
                PONE-D-16-03629
                10.1371/journal.pone.0154662
                4868290
                27182926
                d5684f87-b351-449e-ba3c-d110c5989449
                © 2016 De Luca et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 26 January 2016
                : 15 April 2016
                Page count
                Figures: 2, Tables: 3, Pages: 14
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Antimicrobials
                Antibiotics
                Biology and Life Sciences
                Microbiology
                Microbial Control
                Antimicrobials
                Antibiotics
                Medicine and Health Sciences
                Pediatrics
                Biology and Life Sciences
                Immunology
                Vaccination and Immunization
                Prophylaxis
                Medicine and Health Sciences
                Immunology
                Vaccination and Immunization
                Prophylaxis
                Medicine and Health Sciences
                Public and Occupational Health
                Preventive Medicine
                Vaccination and Immunization
                Prophylaxis
                Biology and Life Sciences
                Developmental Biology
                Neonates
                People and Places
                Population Groupings
                Ethnicities
                Italian People
                Medicine and Health Sciences
                Health Care
                Health Care Facilities
                Hospitals
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Medicine and Health Sciences
                Pediatrics
                Pediatric Infections
                Custom metadata
                All relevant data are within the paper and Supporting Information files.

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