Interventions to reduce infections caused by multidrug resistant Enterobacteriaceae (MDR-E): A systematic review and meta-analysis


      • A systematic review and meta-analysis including 63 studies.
      • Antimicrobial stewardship was found to reduce colonization with MDR-E, but not infection.
      • Decolonization did not result in reduction of MDR-E infection or colonization.



      We aimed to evaluate different interventions to reduce multidrug-resistant Enterobacteriaceae (MDR-E) infection/colonization.


      A systematic review and meta-analysis evaluating interventions for prevention of MDR-E infection/colonization among hospitalized adult patients. The co-primary outcomes were mortality and MDR-E infections. PubMed, Cochrane library, and LILACS databases were searched up till December 2019, as well as grey literature sources. We included randomized controlled trials and observational studies. Infection/colonization/acquisition outcomes were reported per patient-days as pooled incidence ratios (IRs) with 95% confidence intervals (CIs). Interrupted time series (ITS) analysis studies were reported separately.


      Sixty-three studies were included, 16 RCTs, 33 observational studies, and 14 ITS. For the intervention of antimicrobial stewardship program (ASP), 23 studies were included. No differences in mortality or MDR-E infections were observed with ASP, however, MDR-E colonization was significantly reduced (IR 0.69, 95% CI 0.57–0.82). Seventeen studies examined decolonization without significant difference in outcomes. Other interventions were scarcely represented. Among 14 ITS publications, most evaluating ASP, 11 showed benefit of the intervention.


      ASP is an effective measure in preventing MDR-E colonization. Decolonization did not show significant benefit in reducing infection or colonization. Studies are needed to evaluate the cost effectiveness of ASP and assess bundles of interventions.


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      1. WHO, Antimicrobial resistance: global report on surveillance, 2014. WHO n.d. July 18, 2020).

      2. Summary of the latest data on antibiotic resistance in the European Union. European centre for disease prevention and control, 2017. (accessed July 18, 2020).

        • 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 (S28-36)
        • Kohler P.P.
        • Volling C.
        • Green K.
        • Uleryk E.M.
        • Shah P.S.
        • McGeer A.
        Carbapenem resistance, initial antibiotic therapy, and mortality in Klebsiella pneumoniae bacteremia: a systematic review and meta-analysis.
        Infect Control Hosp Epidemiol. 2017; 38: 1319-1328
        • Tacconelli E.
        • Cataldo M.A.
        • Dancer S.J.
        • De Angelis G.
        • Falcone M.
        • Frank U.
        • et al.
        ESCMID guidelines for the management of the infection control measures to reduce transmission of multidrug-resistant Gram-negative bacteria in hospitalized patients.
        Clin Microbiol Infect. 2014; 20 (Suppl 1): 1-55
        • Siegel J.D.
        • Rhinehart E.
        • Jackson M.
        • Chiarello L.
        Healthcare Infection Control Practices Advisory Committee. Management of multidrug-resistant organisms in health care settings.
        Am J Infect Control. 2006; 35 (2007): S165-S193
        • Otter J.A.
        • Mutters N.T.
        • Tacconelli E.
        • Gikas A.
        • Holmes A.H.
        Controversies in guidelines for the control of multidrug-resistant Gram-negative bacteria in EU countries.
        Clin Microbiol Infect. 2015; 21: 1057-1066
      3. Healthcare Facilities | CRE| HAI | CDC 2020. (accessed July 18, 2020).

      4. Systematic review of the effectiveness of infection control measures to prevent the transmission of carbapenemase-producing Enterobacteriaceae through cross-border transfer of patients. European Centre for Disease Prevention and Control, 2014. (accessed July 18, 2020).

        • Baur D.
        • Gladstone B.P.
        • Burkert F.
        • Carrara E.
        • Foschi F.
        • Döbele S.
        Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infection: a systematic review and meta-analysis.
        Lancet Infect Dis. 2017; 17: 990-1001
        • Teerawattanapong N.
        • Kengkla K.
        • Dilokthornsakul P.
        • Saokaew S.
        • Apisarnthanarak A.
        • Chaiyakunapruk N.
        Prevention and control of multidrug-resistant gram-negative bacteria in adult intensive care units: a systematic review and network meta-analysis.
        Clin Infect Dis. 2017; 64: S51-S60
        • Tomczyk S.
        • Zanichelli V.
        • Grayson M.L.
        • Twyman A.
        • Abbas M.
        • Pires D.
        Control of Carbapenem-resistant enterobacteriaceae, acinetobacter baumannii, and pseudomonas aeruginosa in healthcare facilities: a systematic review and reanalysis of quasi-experimental studies.
        Clin Infect Dis. 2019; 68: 873-884
        • Tacconelli E.
        • Mazzaferri F.
        • de Smet A.M.
        • Bragantini D.
        • Eggimann P.
        • Huttner B.D.
        ESCMID-EUCIC clinical guidelines on decolonization of multidrug-resistant Gram-negative bacteria carriers.
        Clin Microbiol Infect. 2019; 25: 807-817
        • Castanheira M.
        • Farrell S.E.
        • Krause K.M.
        • Jones R.N.
        • Sader H.S.
        Contemporary diversity of β-lactamases among Enterobacteriaceae in the nine U.S. census regions and ceftazidime-avibactam activity tested against isolates producing the most prevalent β-lactamase groups.
        Antimicrob Agents Chemother. 2014; 58: 833-838
        • Gales A.C.
        • Castanheira M.
        • Jones R.N.
        • Sader H.S.
        Antimicrobial resistance among Gram-negative bacilli isolated from Latin America: results from SENTRY Antimicrobial Surveillance Program (Latin America, 2008–2010).
        Diagn Microbiol Infect Dis. 2012; 73: 354-360
        • Moher D.
        • Shamseer L.
        • Clarke M.
        • Ghersi D.
        • Liberati A.
        • Petticrew M.
        Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement.
        Syst Rev. 2015; 4: 1
      5. EPOC resources for review authors n.d. /resources/epoc-resources-review-authors (accessed July 18, 2020), 2020.

        • Horan T.C.
        • Andrus M.
        • Dudeck M.A.
        CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting.
        Am J Infect Control. 2008; 36: 309-332
        • Wolkewitz M.
        • Barnett A.G.
        • Palomar Martinez M.
        • Frank U.
        • Schumacher M.
        IMPLEMENT Study Group. Interventions to control nosocomial infections: study designs and statistical issues.
        J Hosp Infect. 2014; 86: 77-82
        • Higgins J.P.T.
        • Thompson S.G.
        • Deeks J.J.
        • Altman D.G.
        Measuring inconsistency in meta-analyses.
        BMJ. 2003; 327: 557-560
      6. Cochrane Handbook for Systematic Reviews of Interventions n.d. /handbook (accessed July 18, 2020), 2020.

        • Daneman N.
        • Sarwar S.
        • Fowler R.A.
        • Cuthbertson B.H.
        • SuDDICU Canadian Study Group
        Effect of selective decontamination on antimicrobial resistance in intensive care units: a systematic review and meta-analysis.
        Lancet Infect Dis. 2013; 13: 328-341
        • Plantinga N.L.
        • de Smet A.M.G.A.
        • Oostdijk E.a.N.
        • de Jonge E.
        • Camus C.
        • Krueger W.A.
        Selective digestive and oropharyngeal decontamination in medical and surgical ICU patients: individual patient data meta-analysis.
        Clin Microbiol Infect. 2018; 24: 505-513
        • Amit S.
        • Mishali H.
        • Kotlovsky T.
        • Schwaber M.J.
        • Carmeli Y.
        Bloodstream infections among carriers of carbapenem-resistant Klebsiella pneumoniae: etiology, incidence and predictors.
        Clin Microbiol Infect. 2015; 21: 30-34
        • Isendahl J.
        • Giske C.G.
        • Hammar U.
        • Sparen P.
        • Tegmark Wisell K.
        • Ternhag A.
        Temporal dynamics and risk factors for bloodstream infection with extended-spectrum β-lactamase-producing bacteria in previously-colonized individuals: national population-based cohort study.
        Clin Infect Dis. 2019; 68: 641-649
        • Tschudin-Sutter S.
        • Lucet J.-C.
        • Mutters N.T.
        • Tacconelli E.
        • Zahar J.R.
        • Harbarth S.
        Contact precautions for preventing nosocomial transmission of extended-spectrum β lactamase-producing escherichia coli: a point/counterpoint review.
        Clin Infect Dis. 2017; 65: 342-347
        • Stone S.P.
        • Cooper B.S.
        • Kibbler C.C.
        • Cookson B.D.
        • Roberts J.A.
        • Medley G.F.
        The ORION statement: guidelines for transparent reporting of outbreak reports and intervention studies of nosocomial infection.
        Lancet Infect Dis. 2007; 7: 282-288
        • George P.
        • Morris A.M.
        Pro/con debate: Should antimicrobial stewardship programs be adopted universally in the intensive care unit?.
        Crit Care. 2010; 14: 205
        • Wolf J.
        • Sun Y.
        • Tang L.
        • Newland J.G.
        • Gerber J.S.
        • Van Dyke C.J.
        Antimicrobial stewardship barriers and goals in pediatric oncology and bone marrow transplantation: a survey of antimicrobial stewardship practitioners.
        Infect Control Hosp Epidemiol. 2016; 37: 343-347