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 beta-lactams, fluoroquinolones and aminoglycosides: colistin MIC = 8 µg/mL; tigecycline MIC = 2 µg/mL; and fosfomycin MIC = 12 µg/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 (figures 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. Disclosures. 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
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Rosa et al. (2016) studied this question.