Advertisement

Inappropriate use of carbapenems in an internal medicine ward: Impact of a carbapenem-focused antimicrobial stewardship program

Published:April 14, 2020DOI:https://doi.org/10.1016/j.ejim.2020.03.017

      Highlights

      • CRE represent a major threat to public health.
      • Carbapenem overuse is a major driver for selection and spread of CRE.
      • ASPs can optimize carbapenem prescribing.
      • Our ASP resulted in over 40% reduction of inappropriate carbapenem use.
      • Carbapenem consumption substantially decreased after ASP implementation (-69.2%).

      Abstract

      Purpose

      Carbapenem consumption is a major driver for selection and spread of carbapenem-resistant Enterobacterales (CRE). We assessed the impact of a carbapenem-focused multimodal antimicrobial stewardship program (ASP) in the internal medicine unit of a medium-size acute-care hospital.

      Methods

      We compared the percentage of inappropriate carbapenem prescriptions and the proportion of carbapenem treated patients registered in a 12-month pre-intervention and in a 24-month post-intervention period by using an interrupted time series analysis. The consumption of carbapenems, expressed in defined daily doses (DDD), was also assessed. As a secondary objective, the incidence of infections by carbapenem-resistant Klebsiella pneumoniae (CRKP) and the percentage of CRKP invasive isolates in the same time periods were compared.

      Results

      After the ASP intervention, the mean monthly percentage of inappropriate carbapenem prescriptions dropped from 59% to 25%, and the mean monthly proportion of carbapenem treated patients decreased from 3% to 1%. The interrupted time series analysis confirmed a significant decrease in the percentage of inappropriate carbapenem prescriptions (-41.6%, p = 0.0262) and in the proportion of carbapenem treated patients (-2.1%, p < 0.0001). Carbapenem consumption decreased from 5.2 to 1.6 DDD x 100 patient-days. The incidence of CRKP infections remained unchanged (29.1 × 100,000 patient-days vs 28.9 × 100,000 patient-days, p = 0.9864) and the percentage of CRKP invasive isolates decreased, though not significantly, from 36.4% to 13.3% (p = 0.3478).

      Conclusions

      The implementation of a carbapenem-focused ASP was effective at limiting the inappropriate use of carbapenems and was associated with a significant decrease in carbapenem consumption. Such effects were sustained during a 24-month post-intervention period.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Hawkey P.M.
        • Livermore D.M.
        Carbapenem antibiotics for serious infections.
        BMJ. 2012; 344 (e3236)
        • Harris P.N.A.
        • Tambyah P.A.
        • Paterson D.L.
        β-lactam and β-lactamase inhibitor combinations in the treatment of extended-spectrum β-lactamase producing Enterobacteriaceae: time for a reappraisal in the era of few antibiotic options?.
        Lancet Infect Dis. 2015; 15: 475-485
      1. European centre for disease prevention and control. Summary of the latest data on antibiotic consumption in the European Union. ESAC-Net Surveillance data; 2017.

        • Van Boeckel T.P.
        • Gandra S.
        • Ashok A.
        • et al.
        Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data.
        Lancet Infect Dis. 2014; 14: 742-750
        • Klein E.Y.
        • Van Boeckel T.P.
        • Martinez E.M.
        • et al.
        Global increase and geographic convergence in antibiotic consumption between 2000 and 2015.
        Proc Natl Acad Sci U S A. 2018; 115: E3463-E3470
        • Gupta N.
        • Limbago B.M.
        • Patel J.B.
        • Kallen A.J.
        Carbapenem-Resistant Enterobacteriaceae: epidemiology and prevention.
        Clin Infect Dis. 2011; 53: 60-67
        • Van Loon K.
        Voor in ‘t holt AF, Vos MC. A systematic review and meta-analyses of the clinical epidemiology of carbapenem-resistant Enterobacteriaceae.
        Antimicrob Agents Chemother. 2017; 62 (e01730-17)
        • Logan L.K.
        • Weinstein R.A..
        The epidemiology of carbapenem-resistant Enterobacteriaceae: the impact and evolution of a global menace.
        J Infect Dis. 2017; 215: 28-36
      2. European Centre for Disease Prevention and Control. Surveillance of antimicrobial resistance in Europe – Annual report of the European Antimicrobial Resistance Surveillance Network (EARS-Net) 2017.
        ECDC, Stockholm2018
        • Cassini A.
        • Högberg L.D.
        • Plachouras D.
        • et al.
        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.
        Lancet Infect Dis. 2019; 19: 56-66
        • Trecarichi E.M.
        • Tumbarello M.
        Therapeutic options for carbapenem-resistant Enterobacteriaceae infections.
        Virulence. 2017; 8: 470-484
        • Martin A.
        • Fahrbach K.
        • Zhao Q.
        • Lodise T.
        Association between carbapenem resistance and mortality among adult, hospitalized patients with serious infections due to Enterobacteriaceae: results of a systematic literature review and meta-analysis.
        Open Forum Infect Dis. 2018; (5:ofy150)
        • Patel N.
        • Harrington S.
        • Dihmess A.
        • et al.
        Clinical epidemiology of carbapenem-intermediate or -resistant Enterobacteriaceae.
        J Antimicrob Chemother. 2011; 66: 1600-1608
        • Marchaim D.
        • Chopra T.
        • Bhargava A.
        • et al.
        Recent exposure to antimicrobials and carbapenem-resistant Enterobacteriaceae: the role of antimicrobial stewardship.
        Infect Control Hosp Epidemiol. 2012; 33: 817-830
        • McLaughlin M.
        • Advincula M.R.
        • Malczynski M.
        • Qi C.
        • Bolon M.
        • Scheetz M.H.
        Correlations of antibiotic use and carbapenem resistance in Enterobacteriaceae.
        Antimicrob Agents Chemother. 2013; 57: 5131-5133
        • ECDC (European Centre for Disease Prevention and Control), EFSA (European Food Safety Authority), and EMA (European Medicines Agency), 2017
        ECDC/EFSA/EMA second_joint_report on the integrated analysis of the consumption of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from humans and food-producing animals – Joint Interagency Antimicrobial Consumption and Resistance Analysis (JIACRA) Report.
        EFSA J. 2017; 15: 4872
        • Wong D.
        • Spellberg B.
        Leveraging antimicrobial stewardship into improving rates of carbapenem-resistant Enterobacteriaceae.
        Virulence. 2017; 8: 383-390
        • Perez F.
        • Van Duin D.
        Carbapenem-resistant Enterobacteriaceae: a menace to our most vulnerable patients.
        Cleve Clin J Med. 2013; 80: 225-233
        • Souli M.
        • Galani I.
        • Antoniadou A.
        • et al.
        An outbreak of infection due to beta-Lactamase Klebsiella pneumoniae Carbapenemase 2–producing K. pneumoniae in a Greek University Hospital: molecular characterization, epidemiology, and outcomes.
        Clin Infect Dis. 2010; 50: 364-373
        • Sotgiu G.
        • Are B.M.
        • Pesapane L.
        • et al.
        Nosocomial transmission of carbapenem-resistant Klebsiella pneumoniae in an Italian university hospital: a molecular epidemiological study.
        J Hosp Infect. 2018; 99: 413-418
        • Iacchini S.
        • Sabbatucci M.
        • Gagliotti C.
        • et al.
        Bloodstream infections due to carbapenemase producing Enterobacteriaceae in Italy: results from nationwide surveillance, 2014 to 2017.
        Euro Surveill. 2019; 24 (pii=1800159)
        • Dellit T.H.
        • Owens R.C.
        • McGowan J.E.
        • et al.
        Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship.
        Clin Infect Dis. 2007; 44: 159-177
        • Spivak E.S.
        • Cosgrove S.E.
        • Srinivasan A.
        Measuring appropriate antimicrobial use: attempts at opening the black box.
        Clin Infect Dis. 2016; 63: 1639-1644
        • Fortini A.
        • Faraone A.
        • Di Pietro M.
        • et al.
        Antimicrobial stewardship in an Internal Medicine ward: effects on antibiotic consumption and on the use of carbapenems.
        Intern Emerg Med. 2018; 13: 1219-1226
        • Davey P.
        • Marwick C.A.
        • Scott C.L.
        • et al.
        Interventions to improve antibiotic prescribing practices for hospital inpatients.
        Cochrane Database Systematic Rev. 2017; (Art. No.: CD003543)
        • García-Rodríguez J.F.
        • Bardán-García B.
        • Peña-Rodríguez M.F.
        • Álvarez-Díaz H.
        • Mariño-Callejo A.
        Meropenem antimicrobial stewardship program: clinical, economic, and antibiotic resistance impact.
        Eur J Clin Microbiol Infect Dis. 2019; 38: 161-170
        • Janssen J.
        • Kinkade A.
        • Man D.
        CARBapenem utilizatiON evaluation in a large community hospital (CARBON): a quality improvement study.
        Can J Hosp Pharm. 2015; 68: 327-331
        • Rhodes A.
        • Evans L.E.
        • Alhazzani W.
        • et al.
        Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016.
        Intensive Care Med. 2017; 43: 304-377
      3. IDSA sepsis task force infectious diseases society of America (IDSA) position statement: why idsa did not endorse the surviving sepsis campaign guidelines.
        Clin Infect Dis. 2018; 66: 1631-1635
        • Klompas M.
        • Calandra T.
        • Singer M.
        Antibiotics for sepsis—finding the equilibrium.
        JAMA. 2018; 320: 1433-1434
        • Kollef M.H.
        • Burnham J.P.
        Antibiotic thresholds for sepsis and septic shock.
        Clin Infect Dis. 2018; (Dec 7)
        • DePestel D.D.
        • Eiland III, E.H.
        • Lusardi K.
        • et al.
        Assessing appropriateness of antimicrobial therapy: in the eye of the interpreter.
        Clin Infect Dis. 2014; 59: 154-161
        • Cisneros J.M.
        • Neth O.
        • Gil-Navarro M.V.
        • et al.
        Global impact of an educational antimicrobial stewardship programme on prescribing practice in a tertiary hospital centre.
        Clin Microbiol Infect. 2014; 20: 82-88
      4. European centre for disease prevention and control. Antimicrobial consumption.
        ECDC. Annual epidemiological report 2017. ECDC, Stockholm2018
        • Bitterman R.
        • Hussein K.
        • Leibovici L.
        • Carmeli Y.
        • Paul M.
        Systematic review of antibiotic consumption in acute care hospitals.
        Clin Microbiol Infect. 2016; 22 (e7–561.e19): 561
        • Grundmann H.
        • Glasner C.
        • Albiger B.
        • et al.
        Occurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE): a prospective, multinational study.
        Lancet Infect Dis. 2017; 17: 153-163
      5. Facility Guidance for Control of Carbapenem- Resistant Enterobacteriaceae (CRE) November 2015 Update - CRE toolkit. Centers for Disease Control and Prevention.

        • Marra A.R.
        • de Almeida S.M.
        • Correa L.
        • et al.
        The effect of limiting antimicrobial therapy duration on antimicrobial resistance in the critical care setting.
        Am J Infect Control. 2009; 37: 204-209
        • Giacobbe D.R.
        • Del Bono V.
        • Mikulska M.
        • et al.
        Impact of a mixed educational and semi-restrictive antimicrobial stewardship project in a large teaching hospital in Northern Italy.
        Infection. 2017; 45: 849-856
      6. Piano Nazionale di Contrasto dell'Antimicrobico-Resistenza (PNCAR) 2017–2020. Ministero della Salute (October 2017). http://www.salute.gov.it/imgs/C_17_pubblicazioni_2660_allegato.pdf.

      7. Guidelines for the prevention and control of carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa in health care facilities.
        World Health Organization, Geneva2017 (Licence: CC BY-NC-SA 3.0 IGO)
      8. Indicazioni operative per il controllo della trasmissione di enterobatteri resistenti ai carbapenemi (CRE) produttori di carbapenemasi (CPE). DECRETO 23 ottobre 2019, n. 17278. 30.10.2019 - BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N. 44.

      9. Indicazioni regionali per il contrasto della trasmissione di Enterobacterales produttori di metallo- betalattamasi di tipo New-Delhi.DECRETO 26 luglio 2019, n. 12772. 7.8.2019 - BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N. 32.

        • Ourghanlian C.
        • Caruba T.
        • Facchin A.
        • et al.
        Improvement of antibiotic therapy adequacy with local guidelines and their reassessment through a multidisciplinary action: Prospective study in an Internal Medicine department.
        Rev Med Interne. 2020; 41: 8-13https://doi.org/10.1016/j.revmed.2019.09.002
        • Bolla C.
        • Di Pietrantonj C.
        • Ferrando E.
        • et al.
        Example of antimicrobial stewardship program in a community hospital in Italy.
        Med Mal Infect. 2019 Dec 14; (pii: S0399-077X(19)31076-5)https://doi.org/10.1016/j.medmal.2019.11.008