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Barbara Fiori,1–3,* Tiziana D’Inzeo,2,3,* Brunella Posteraro,4,5 Giulia Menchinelli,3 Flora Marzia Liotti,3 Giulia De Angelis,2,3 Flavio De Maio,3 Massimo Fantoni,6,7 Rita Murri,6,7 Giancarlo Scoppettuolo,6 Giulio Ventura,6 Mario Tumbarello,6,7 Francesco Pennestrì,4 Francesco Taccari,7 Maurizio Sanguinetti,2,3 Teresa Spanu2,31Scuola Provinciale Superiore di Sanità Claudiana, Bolzano, Italy; 2Fondazione Policlinico Universitario A. Gemelli IRCCS, Dipartimento di Scienze di Laboratorio e Infettivologiche, Rome, Italy; 3Università Cattolica del Sacro Cuore, Istituto di Microbiologia, Rome, Italy; 4Fondazione Policlinico Universitario A. Gemelli IRCCS, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Rome, Italy; 5Università Cattolica del Sacro Cuore Rome, Istituto di Patologia e Semeiotica Medica, Rome, Italy; 6Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC Malattie Infettive, Rome, Italy; 7Istituto di Malattie Infettive, Università Cattolica del Sacro Cuore, Rome, Italy*These authors contributed equally to this workObjectives: To describe a rapid workflow based on the direct detection of Escherichia coli (Ec) and Klebsiella pneumoniae (Kp) producing CTX-M extended-spectrum β-lactamase (ESBL) and/or carbapenemases (eg, KPC, VIM) from blood cultures (BCs) and the infectious disease (ID) consulting for timely appropriate antimicrobial therapy.Methods: This observational, retrospective study included adult patients with a first episode of Ec or Kp bloodstream infection (BSI) in a large Italian university hospital, where an inpatient ID consultation team (IDCT) has been operational. Results from the BCs tested for detecting blaCTX-M, blaKPC, blaNDM, blaOXA-48-like, and blaVIM genes by the eazyplex®, SuperBug CRE assay in Ec and Kp organisms had been notified for antimicrobial therapy consulting.Results: In 321 BSI episodes studied, we found that 151 (47.0%) of Ec or Kp organisms harbored blaCTX-M and/or blaKPC and/or blaVIM (meantime from BC collection: 18.5 h). Empirical antimicrobial treatment was appropriate in 21.8% (33/151) of BSIs, namely 5.9% (3/51) of BSIs caused by KPC/VIM producers and 30.0% (30/100) of BSIs caused by CTX-M producers. After notification of results, the IDCT modified antimicrobial therapy (mean time from BC collection: 20 h) such that the proportion of appropriate treatments increased to 84.8% (128/151) of BSIs, namely 70.6% (36/51) of BSIs caused by KPC/VIM producers and 92.0% (92/100) of BSIs caused by CTX-M producers.Conclusion: Our study shows that a rapid diagnostic-driven clinical strategy allowed for early prescription of potentially effective antimicrobial therapy in BSIs caused by CTX-M ESBL- and/or KPC/VIM carbapenemase-producing Ec and Kp organisms.Keywords: Escherichia coli, Klebsiella pneumoniae, bloodstream infection, drug resistance, targeted therapy, infectious disease consultation

Objectives: To describe a rapid workflow based on the direct detection of Escherichia coli ( Ec ) and Klebsiella pneumoniae ( Kp ) producing CTX-M extended-spectrum β-lactamase (ESBL) and/or carbapenemases (eg, KPC, VIM) from blood cultures (BCs) and the infectious disease (ID) consulting for timely appropriate antimicrobial therapy. Methods: This observational, retrospective study included adult patients with a first episode of Ec or Kp bloodstream infection (BSI) in a large Italian university hospital, where an inpatient ID consultation team (IDCT) has been operational. Results from the BCs tested for detecting bla CTX-M , bla KPC , bla NDM , bla OXA-48-like , and bla VIM genes by the eazyplex ® SuperBug CRE assay in Ec and Kp organisms had been notified for antimicrobial therapy consulting. Results: In 321 BSI episodes studied, we found that 151 (47.0%) of Ec or Kp organisms harbored bla CTX-M and/or bla KPC and/or bla VIM (meantime from BC collection: 18.5 h). Empirical antimicrobial treatment was appropriate in 21.8% (33/151) of BSIs, namely 5.9% (3/51) of BSIs caused by KPC/VIM producers and 30.0% (30/100) of BSIs caused by CTX-M producers. After notification of results, the IDCT modified antimicrobial therapy (mean time from BC collection: 20 h) such that the proportion of appropriate treatments increased to 84.8% (128/151) of BSIs, namely 70.6% (36/51) of BSIs caused by KPC/VIM producers and 92.0% (92/100) of BSIs caused by CTX-M producers. Conclusion: Our study shows that a rapid diagnostic-driven clinical strategy allowed for early prescription of potentially effective antimicrobial therapy in BSIs caused by CTX-M ESBL- and/or KPC/VIM carbapenemase-producing Ec and Kp organisms., Competing Interests: The authors report no conflicts of interest in this work.