Major article| Volume 41, ISSUE 12, P1167-1172, December 2013

Download started.


Eradication of carbapenem-resistant Enterobacteriaceae gastrointestinal colonization with nonabsorbable oral antibiotic treatment: A prospective controlled trial


      Carbapenem-resistant Enterobacteriaceae (CRE) are emerging. In attempt to eradicate CRE colonization, we conducted a semirandomized, prospective, controlled trial using oral nonabsorbable antibiotics.


      Consecutive hospitalized CRE carriers were studied. Patients whose rectal isolates were gentamicin sensitive but colistin resistant were treated with gentamicin. Patients whose isolates were colistin sensitive but gentamicin resistant were treated with colistin. Patients whose isolates were sensitive to both drugs were randomized to 3 groups of oral antibiotic treatment: gentamicin, colistin, or both. Patients whose isolates were resistant to both drugs, and those who did not consent, were followed for spontaneous eradication.


      One hundred fifty-two patients were included; 102 were followed for spontaneous eradication for a median duration of 140 days (controls), and 50 received 1 of the 3 drug regimens: gentamicin, 26; colistin, 16; both drugs, 8, followed for a median duration of 33 days. Eradication rates in the 3 treatment groups were 42%, 50%, and 37.5%, respectively, each significantly higher than the 7% spontaneous eradication rate in the control group (P < .001, P < .001, and P = .004, respectively) with no difference between the regimens. No significant adverse effects were observed.


      Oral antibiotic treatment with nonabsorbable drugs to which CRE is susceptible appears to be an effective and safe for eradication of CRE colonization and, thereby, may reduce patient-to-patient transmission and incidence of clinical infection with this difficult-to-treat organism.

      Key Words

      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 to American Journal of Infection Control
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Deshpande L.M.
        • Jones R.N.
        • Fritsche T.R.
        • Sader H.S.
        Occurrence and characterization of carbapenemase-producing Enterobacteriaceae: report from the SENTRY Antimicrobial Surveillance Program (2000-2004).
        Microb Drug Resist. 2006; 12: 223-230
        • Nordmann P.
        • Cuzon G.
        • Naas T.
        The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria.
        Lancet Infect Dis. 2009; 9: 228-236
        • Samra Z.
        • Ofir O.
        • Lishtzinsky Y.
        • Madar-Shapiro L.
        • Bishara J.
        Outbreak of carbapenem-resistant Klebsiella pneumoniae producing KPC-3 in a tertiary medical centre in Israel.
        Int J Antimicrob Agents. 2007; 30: 525-529
        • Leavitt A.
        • Navon-Venezia S.
        • Chmelnitsky I.
        • Schwaber M.J.
        • Carmeli Y.
        Emergence of KPC-2 and KPC-3 in carbapenem-resistant Klebsiella pneumoniae strains in an Israeli hospital.
        Antimicrob Agents Chemother. 2007; 51: 3026-3029
        • Hussein K.
        • Sprecher H.
        • Mashiach T.
        • Oren I.
        • Kassis I.
        • Finkelstein R.
        Carbapenem resistance among Klebsiella pneumoniae isolates: risk factors, molecular characteristics, and susceptibility patterns.
        Infect Control Hosp Epidemiol. 2009; 30: 666-671
        • Falagas M.E.
        • Karageorgopoulos D.E.
        • Nordmann P.
        Therapeutic options for infections with Enterobacteriaceae producing carbapenem-hydrolyzing enzymes.
        Future Microbiol. 2011; 6: 653-666
        • Livermore D.M.
        • Warner M.
        • Mushtaq S.
        • Dumith M.
        • Zhang J.
        • Woodford N.
        What remains against carbapenem-resistant Enterobacteriaceae? Evaluation of chloramphenicol, ciprofloxacin, colistin, fosfomycin, minocycline, nitrofurantoin, temocillin and tigecycline.
        Int J Antimicrob Agents. 2011; 37: 415-419
        • Borer A.
        • Saidel-Odes L.
        • Riesenberg K.
        • Eskira S.
        • Peled N.
        • Nativ R.
        • et al.
        Attributable mortality rate for carbapenem-resistant Klebsiella pneumoniae bacteremia.
        Infect Control Hosp Epidemiol. 2009; 30: 972-976
      1. Guidance for control of infections with carbapenem-resistant or carbapenemase-producing Enterobacteriaceae in acute care facilities.
        MMWR Morb Mortal Wkly Rep. 2009; 58: 256-260
        • Troche G.
        • Joly L.M.
        • Guibert M.
        • Zazzo J.
        Detection and treatment of antibiotic-resistant bacterial carriage in a surgical intensive care unit: a 6-year prospective survey.
        Infect Control Hosp Epidemiol. 2005; 26: 161-165
        • Paterson D.L.
        • Singh N.
        • Rihs J.D.
        • Squier C.
        • Rihs B.L.
        • Muder R.R.
        Control of an outbreak of infection due to extended-spectrum β-lactamase-producing Escherichia coli in a liver transplantation unit.
        Clin Infect Dis. 2001; 33: 126-128
        • de Jonge E.
        • Schultz M.J.
        • Spanjaard L.
        • Bossuyt P.M.
        • Vroom M.B.
        • Dankert J.
        • et al.
        Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial.
        Lancet. 2003; 362: 1011-1016
        • Brun-Buisson C.
        • Legrand P.
        • Rauss A.
        • Richard C.
        • Montravers F.
        • Besbes M.
        • et al.
        Intestinal decontamination for control of nosocomial multiresistant gram-negative bacilli: study of an outbreak in an intensive care unit.
        Ann Intern Med. 1989; 110: 873-881
        • Taylor M.E.
        • Oppenheim B.A.
        Selective decontamination of the gastrointestinal tract as an infection control measure.
        J Hosp Infect. 1991; 17: 271-278
        • Zuckerman T.
        • Benyamini N.
        • Sprecher H.
        • Fineman R.
        • Finkelstein R.
        • Rowe J.M.
        • et al.
        SCT in patients with carbapenem-resistant Klebsiella pneumoniae: a single center experience with oral gentamicin for the eradication of carrier state.
        Bone Marrow Transplant. 2011; 46: 1226-1230
        • Kotlovsky T.
        • Shalginov R.
        • Austin L.
        • Sprecher H.
        Rapid detection of bla(KPC)-positive Klebsiella pneumoniae in a clinical setting.
        Eur J Clin Microbiol Infect Dis. 2009; 28: 309-311
        • Clinical and Laboratory Standards Institute
        Performance standards for antimicrobial susceptibility testing; 20th informational supplement. CLSI document M100–S20.
        Clinical and Laboratory Standards Institute, Wayne [PA]2010
      2. European Committee on Antimicrobial Susceptibility Testing. Clinical breakpoint tables v. 1.3, 2011. Available from: Accessed January 5, 2011.

        • Rudnic E.M.
        • Schwartz J.D.
        Oral solid dosage forms. In: Gennaro JP.
        in: Remington: the science and practice of pharmacy. Lippincott Williams and Wilkins, Baltimore [MD]2000: 858-893
        • Bratu S.
        • Landman D.
        • Haag R.
        • Recco R.
        • Eramo A.
        • Alam M.
        • et al.
        Rapid spread of carbapenem-resistant Klebsiella pneumoniae in New York City: a new threat to our antibiotic armamentarium.
        Arch Intern Med. 2005; 165: 1430-1435
        • Ben-David D.
        • Maor Y.
        • Keller N.
        • Regev-Yochay G.
        • Tal I.
        • Shachar D.
        • et al.
        Potential role of active surveillance in the control of a hospital-wide outbreak of carbapenem-resistant Klebsiella pneumoniae infection.
        Infect Control Hosp Epidemiol. 2010; 31: 620-626
        • Patel G.
        • Huprikar S.
        • Factor S.H.
        • Jenkins S.G.
        • Calfee D.P.
        Outcomes of carbapenem-resistant Klebsiella pneumoniae infection and the impact of antimicrobial and adjunctive therapies.
        Infect Control Hosp Epidemiol. 2008; 29: 1099-1106
        • Schwaber M.J.
        • Klarfeld-Lidji S.
        • Navon-Venezia S.
        • Schwartz D.
        • Leavitt A.
        • Carmeli Y.
        Predictors of carbapenem-resistant Klebsiella pneumoniae acquisition among hospitalized adults and effect of acquisition on mortality.
        Antimicrob Agents Chemother. 2008; 52: 1028-1033
        • Daikos G.L.
        • Petrikkos P.
        • Psichogiou M.
        • Kosmidis C.
        • Vryonis E.
        • Skoutelis A.
        • et al.
        Prospective observational study of the impact of VIM-1 metallo-β-lactamase on the outcome of patients with Klebsiella pneumoniae bloodstream infections.
        Antimicrob Agents Chemother. 2009; 53: 1868-1873
        • Souli M.
        • Galani I.
        • Antoniadou A.
        • Papadomichelakis E.
        • Poulakou G.
        • Panagea T.
        • et al.
        An outbreak of infection due to β-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
        • Schwaber M.J.
        • Lev B.
        • Israeli A.
        • Solter E.
        • Smollan G.
        • Rubinovitch B.
        • et al.
        Containment of a country-wide outbreak of carbapenem-resistant Klebsiella pneumoniae in Israeli hospitals via a nationally implemented intervention.
        Clin Infect Dis. 2011; 52: 848-855
        • Gupta N.
        • Limbago B.M.
        • Patel J.B.
        • Kallen A.J.
        Carbapenem-resistant Enterobacteriaceae: epidemiology and prevention.
        Clin Infect Dis. 2011; 53: 60-67
        • Silvestri L.
        • Kerr S.
        • Gullo A.
        Prevention of infection using selective decontamination of the digestive tract.
        in: Saene H.K.F. Silversti L. de la Cal M.A. Infection control in the intensive care unit. 2nd ed. Springer, Milan2005: 297-312
        • Saidel-Odes L.
        • Polachek H.
        • Peled N.
        • Riesenberg K.
        • Schlaeffer F.
        • Trabelsi Y.
        • et al.
        A randomized, double-blind, placebo-controlled trial of selective digestive decontamination using oral gentamicin and oral polymyxin E for eradication of carbapenem-resistant Klebsiella pneumoniae carriage.
        Infect Control Hosp Epidemiol. 2012; 33: 14-19
        • Perez F.
        • Pultz M.J.
        • Endimiani A.
        • Bonomo R.A.
        • Donskey C.J.
        Effect of antibiotic treatment on establishment and elimination of intestinal colonization by KPC-producing Klebsiella pneumoniae in mice.
        Antimicrob Agents Chemother. 2011; 55: 2585-2589
        • Zimmerman F.S.
        • Assous M.V.
        • Bdolah-Abram T.
        • Lachish T.
        • Yinnon A.M.
        • Wiener-Well Y.
        Duration of carriage of carbapenem-resistant Enterobacteriaceae following hospital discharge.
        Am J Infect Control. 2013; 41: 190-194