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      Do specific antimicrobial stewardship interventions have an impact on carbapenem resistance in Gram-negative bacilli? A multicentre quasi-experimental ecological study: time-trend analysis and characterization of carbapenemases

      1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 2 , 10 , 11 , 12 , 13 , 4 , 1 , 1 , 2 , 1 , , , , , , , , , , , , , , , the CarbaPIRASOA team
      Journal of Antimicrobial Chemotherapy
      Oxford University Press (OUP)

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          Abstract

          Background

          Carbapenem-resistant Gram-negative bacilli (CR-GNB) are among the most threatening microorganisms worldwide and carbapenem use facilitates their spread. Antimicrobial stewardship programmes (ASPs) can help to optimize the use of antibiotics. This study evaluates the impact of a multifaceted educational ASP on carbapenem use and on the epidemiology of CR-GNB.

          Methods

          We conducted a quasi-experimental, time-series study in seven hospitals, from January 2014 to September 2018. The key intervention was composed of educational interviews promoting the appropriate use of carbapenems. The primary endpoints were carbapenem consumption and incidence density (ID) of CR-GNB. All non-duplicated CR-GNB clinical isolates were tested using phenotypic assays and PCR for the presence of carbapenemases. Joinpoint regression and interrupted time-series analyses were used to determine trends.

          Results

          A decrease in carbapenem consumption throughout the study period [average quarterly percentage change (AQPC) −1.5%, P < 0.001] and a −8.170 (−16.064 to −0.277) level change following the intervention were observed. The ID of CR-Acinetobacter baumannii decreased (AQPC −3.5%, P = 0.02) and the overall ID of CR-GNB remained stable (AQPC −0.4%, P = 0.52). CR-GNB, CR-Pseudomonas aeruginosa and CR-A. baumannii IDs per hospital correlated with the local consumption of carbapenems. The most prevalent carbapenem resistance mechanisms were OXA-23 for CR-A. baumannii (76.1%), OXA-48 for CR-Klebsiella pneumoniae (66%) and no carbapenemases for CR-P. aeruginosa (91.7%). The epidemiology of carbapenemases was heterogeneous throughout the study, especially for carbapenemase-producing Enterobacteriaceae.

          Conclusions

          In conclusion, a multifaceted, educational interview-based ASP targeting carbapenem prescribing reduced carbapenem use and the ID of CR-A. baumannii.

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          Most cited references23

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          Permutation tests for joinpoint regression with applications to cancer rates

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            Use of interrupted time series analysis in evaluating health care quality improvements.

            Interrupted time series (ITS) analysis is arguably the strongest quasi-experimental research design. ITS is particularly useful when a randomized trial is infeasible or unethical. The approach usually involves constructing a time series of population-level rates for a particular quality improvement focus (eg, rates of attention-deficit/hyperactivity disorder [ADHD] medication initiation) and testing statistically for a change in the outcome rate in the time periods before and time periods after implementation of a policy/program designed to change the outcome. In parallel, investigators often analyze rates of negative outcomes that might be (unintentionally) affected by the policy/program. We discuss why ITS is a useful tool for quality improvement. Strengths of ITS include the ability to control for secular trends in the data (unlike a 2-period before-and-after t test), ability to evaluate outcomes using population-level data, clear graphical presentation of results, ease of conducting stratified analyses, and ability to evaluate both intended and unintended consequences of interventions. Limitations of ITS include the need for a minimum of 8 time periods before and 8 after an intervention to evaluate changes statistically, difficulty in analyzing the independent impact of separate components of a program that are implemented close together in time, and existence of a suitable control population. Investigators must also be careful not to make individual-level inferences when population-level rates are used to evaluate interventions (though ITS can be used with individual-level data). A brief description of ITS is provided, including a fully implemented (but hypothetical) study of the impact of a program to reduce ADHD medication initiation in children younger than 5 years old and insured by Medicaid in Washington State. An example of the database needed to conduct an ITS is provided, as well as SAS code to implement a difference-in-differences model using preschool-age children in California as a comparison group. Copyright © 2013 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.
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              Interventions to improve antibiotic prescribing practices for hospital inpatients.

              Antibiotic resistance is a major public health problem. Infections caused by multidrug-resistant bacteria are associated with prolonged hospital stay and death compared with infections caused by susceptible bacteria. Appropriate antibiotic use in hospitals should ensure effective treatment of patients with infection and reduce unnecessary prescriptions. We updated this systematic review to evaluate the impact of interventions to improve antibiotic prescribing to hospital inpatients.
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                Author and article information

                Contributors
                (View ORCID Profile)
                (View ORCID Profile)
                Journal
                Journal of Antimicrobial Chemotherapy
                Oxford University Press (OUP)
                0305-7453
                1460-2091
                July 01 2021
                June 18 2021
                March 26 2021
                July 01 2021
                June 18 2021
                March 26 2021
                : 76
                : 7
                : 1928-1936
                Affiliations
                [1 ]Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen del Rocio/CSIC/University of Seville/Institute of Biomedicine of Seville (IBiS), Seville, Spain
                [2 ]Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen Macarena, Department of Microbiology, University of Seville, Institute of Biomedicine of Seville (IBiS), Seville, Spain
                [3 ]Clinical Unit of Internal Medicine, University Hospital Puerta del Mar, Cadiz, Spain
                [4 ]Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedical Research of Malaga (IBIMA), Regional University Hospital of Malaga, Malaga, Spain
                [5 ]Department of Microbiology, University Hospital Virgen de las Nieves, Granada, Spain
                [6 ]Clinical Unit of Infectious Diseases, Hospital San Cecilio, Granada, Spain
                [7 ]Clinical Unit of Infectious Diseases, Hospital Complex of Jaen, Jaen, Spain
                [8 ]Department of Microbiology, Hospital Virgen de la Victoria, Malaga, Spain
                [9 ]Clinical Unit of Internal Medicine, Department of Infectious Diseases, Hospital Torrecardenas, Almeria, Spain
                [10 ]Department of Microbiology, Hospital Complex of Jaen, Jaen, Spain
                [11 ]Clinical Unit of Infectious Diseases, Hospital Virgen de la Victoria, Malaga, Spain
                [12 ]Department of Microbiology, Hospital Torrecardenas, Almeria, Spain
                [13 ]Department of Microbiology, University Hospital Puerta del Mar, Cadiz, Spain
                Article
                10.1093/jac/dkab073
                33769481
                5ef304b9-6971-4052-93dc-0b1f12f3de4e
                © 2021

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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