Klebsiella pneumoniae in a Multivisceral Transplant Candidate">
2032. Application of "Precision Medicine" Through the Molecular Characterization of Extensively Drug Resistant (XDR) Klebsiella pneumoniae in a Multivisceral Transplant Candidate
Session: Poster Abstract Session: Antimicrobial Resistant Infections: Treatment
Saturday, October 29, 2016
Room: Poster Hall
  • Kpn_IDW_poster_10222016.pdf (825.1 kB)
  • Background: Treatment of carbapenemase-producing organisms is clinically challenging. We elucidated the mechanisms of carbapenem resistance in order to design an effective antibiotic regimen for a patient with XDR K. pneumoniae

    Methods: A K. pneumoniae isolate was recovered as a cause of complicated urinary tract infection in a patient undergoing evaluation for multi-visceral transplantation. The patient, originally from Turkey, required multiple bowel resections for the treatment of a desmoid tumor. Antimicrobial susceptibility (AST) testing was performed using the Vitek-automated system and Etest. The CarbaNP assay was used to detect carbapenemases, followed by amplification of bla genes with PCR and sequencing. Multilocus sequence typing (MLST) and plasmid replicon typing were performed. Antibiotic combinations were tested using disk diffusion and Etest.

    Results: AST demonstrated resistance to all b-lactams, fluoroquinolones and aminoglycosides: colistin MIC = 8 µg/mL; tigecycline MIC = 2µg/mL; and fosfomycin MIC = 12µg/mL. CarbaNP detected a carbapenemase. PCR amplification and DNA sequencing revealed presence of blaNDM-1, blaOXA-48, and blaCTX-M. MLST determined that the isolate belonged to sequence type (ST) 14. Three different plasmids were identified containing blaNDM-1, blaOXA-48/blaCTX-M, and blaCTX-M. Combination of ceftazidime-avibactam (TAZ-AVI) plus aztreonam, both by disk diffusion and Etest suggested synergy (Figure 1 and 2). The patient initially received empirical treatment with oral fosfomycin and IV meropenem/ertapenem with eradication of the XDR K. pneumoniae in the urine. Subsequently, TAZ-AVI/aztreonam were used as part of peri-operative antibiotic prophylaxis effectively preventing post-surgical infections with XDR K. pneumoniae, despite persistent rectal colonization with this organism.

    Conclusion: K. pneumoniae harboring blaNDM-1 and blaOXA-48 is being increasingly recognized in the US and globally. Molecular characterization of the genetic background and mechanisms of resistance in this isolate, precision medicine, guided the design of an effective antibiotic regimen (TAZ-AVI/aztreonam) for prevention of infections with XDR K. pneumoniae.

    Rossana Rosa, MD, Department of Medicine, Jackson Memorial Hospital-University of Miami Miller School of Medicine, Miami, FL, Susan D. Rudin, BS, Case Western Reserve University, Cleveland, OH; Research Service Louis Stokes Cleveland VAMC, Cleveland, OH, Laura J. Rojas, MSc, Case Western Reserve University/Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, Armando Perez-Cardona, BS, Jackson Memorial Hospital, Miami, FL, Laura Aragon, PharmD, BCPS-AQ ID, Pharmacy, Jackson Memorial Hospital, Miami, FL, David P. Nicolau, PharmD, FCCP, FIDSA, Center for Anti-Infective Research & Development at Hartford Hospital, Hartford, CT, Federico Perez, MD, Louis Stokes Cleveland VA M, Cleveland, OH, Robert A. Bonomo, MD, Pharmacology, Molecular Biology, and Microbiology, Case Western Reserve University, Cleveland, OH, Octavio Martinez, PhD, Pathology, University of Miami Miller School of Medicine, Miami, FL, Jose Camargo, MD, Medicine, University of Miami Miller School of Medicine, Miami, FL and Lilian Abbo, MD, FIDSA, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL


    R. Rosa, None

    S. D. Rudin, None

    L. J. Rojas, None

    A. Perez-Cardona, None

    L. Aragon, None

    D. P. Nicolau, None

    F. Perez, Pfizer: Grant Investigator , Grant recipient
    Actavis: Consultant , Consulting fee

    R. A. Bonomo, Merck: Grant Investigator and Scientific Advisor , Consulting fee and Research grant
    Actavis: Invited Speaker , Speaker honorarium
    Allergan: Grant Investigator , Research grant
    Wockhardt: Grant Investigator , Research grant
    GlaxoSmithKline: Grant Investigator , Research grant
    AstraZeneca: Grant Investigator , Research grant

    O. Martinez, None

    J. Camargo, None

    L. Abbo, None

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.