1964. Microbiological Outcomes with Plazomicin (PLZ) versus Colistin (CST) in Patients (pts) with Bloodstream Infections (BSI) Caused by Carbapenem-resistant Enterobacteriaceae (CRE) in the CARE Study
Session: Poster Abstract Session: Clinical Trials
Saturday, October 6, 2018
Room: S Poster Hall
Posters
  • 1964_IDWeek Serio Poster_F.pdf (201.8 kB)
  • Background: PLZ is a next-generation aminoglycoside with structural modifications that protect it from aminoglycoside-modifying enzymes (AMEs) and in vitro activity against multidrug-resistant (MDR) Enterobacteriaceae, including aminoglycoside- and carbapenem-resistant strains. In the CARE study, PLZ was associated with improvement in 28-day all-cause mortality vs CST in pts with CRE BSI. We report the microbiological outcomes in the CARE study by pathogen and key resistance mechanism.

    Methods: CARE was a multinational, open-label trial that enrolled BSI pts with documented or presumed CRE into 2 cohorts. Pts in the randomized cohort received PLZ (15 mg/kg q24h IV) or CST (300-mg load [CST base activity] then 5 mg/kg/d IV) plus adjunctive tigecycline or meropenem. Pts in the observational cohort received PLZ plus investigator’s choice of adjunctive agent. Treatment duration was 7-14 days. Isolate identification and susceptibility testing were conducted by a central laboratory. Whole-genome sequencing was used to identify AME and carbapenemase genes. Microbiological outcomes were assessed in pts with confirmed CRE who received ≥1 dose of study drug (mMITT population).

    Results: Of 45 BSI pts enrolled, 43 had confirmed CRE (mMITT), including Klebsiella pneumoniae (n = 42) and Enterobacter aerogenes (n = 1). Against CRE, PLZ MICs ranged from 0.12 to >128 µg/mL; 25/28 (89.3%) isolates from PLZ-treated pts had a PLZ MIC ≤4 µg/mL, while 3 had a PLZ MIC ≥128 µg/mL and a confirmed 16S ribosomal methyltransferase gene. CST MICs ranged from 0.25 to >128 µg/mL; 6/16 (37.5%) isolates from CST-treated pts had an MIC >2 µg/mL. There were 47 distinct Enterobacteriaceae pathogens isolated from 43 patients, and of these, AME genes were detected in 43/47 (91.5%), most commonly aac(6’)-Ib (n = 29). Carbapenemase genes were detected in 45/47 (95.7%) isolates, most commonly blaKPC (n = 33). PLZ demonstrated higher microbiological eradication rates than CST against CRE, including AME- and carbapenemase-producing isolates (Table).

    Conclusion: The results provide evidence of the efficacy of PLZ-based therapy for pts with BSI due to MDR Enterobacteriaceae, including AME- and carbapenemase-producing organisms.

    Alisa W. Serio, PhD1, Alex Smith, MS1, Kevin M. Krause, MBA1, Irene Galani, PhD2, Ana Cristina Gales, MD, PhD3, Adrian Jubb, MBChB, PhD, FRCPath1 and Lynn E. Connolly, MD, PhD1, (1)Achaogen, Inc., South San Francisco, CA, (2)Infectious Diseases Research Laboratory, 4th Department of Internal Medicine, University General Hospital Attikon, National and Kapodistrian University of Athens, Athens, Greece, (3)Division of Infectious Diseases, Department of Internal Medicine, Escola Paulista de Medicina/Universidade Federal de São Paulo (EPM/UNIFESP), São Paulo, Brazil

    Disclosures:

    A. W. Serio, Achaogen, Inc.: Employee and Shareholder , Salary .

    A. Smith, Achaogen, Inc.: Employee and Shareholder , Salary .

    K. M. Krause, Achaogen, Inc.: Employee , Salary .

    I. Galani, Achaogen, Inc.: Scientific Advisor , Research funding and honoraria . MSD: Scientific Advisor , Honoraria .

    A. C. Gales, MSD: Consultant and Speaker , Consulting fee . Pfizer: Consultant and Speaker , Consulting fee . BD: Consultant , Consulting fee . Bayer: Consultant , Consulting fee .

    A. Jubb, Achaogen, Inc.: Employee and Shareholder , Salary .

    L. E. Connolly, Achaogen, Inc.: Consultant , Consulting fee .

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