1359. Activity of Meropenem/Nacubactam Combination against Gram-negative Clinical Isolates: ROSCO Global Surveillance 2017
Session: Poster Abstract Session: Novel Agents
Friday, October 5, 2018
Room: S Poster Hall
Posters
  • Poster 1359_IDweek2018.pdf (398.6 kB)
  • Background: Nacubactam (NAC, OP0595, RG6080) is a novel member of the diazabicyclooctane inhibitor family with a dual mode of action, acting as a β-lactamase inhibitor and an antibacterial agent by means of PBP2 inactivation. NAC restores and extends the activity of β-lactam antibiotics, such as meropenem (MEM), when used in combination against a variety of carbapenem-resistant Enterobacteriaceae (CRE). The first year results of the ROSCO surveillance study for MEM/NAC against contemporary clinical isolates are presented here.

    Methods: Isolates (n=4695) collected in 2017 from 50 sites in US and European hospitals included 30 different species of Enterobacteriaceae (EB, n=3306), Pseudomonas spp. (n=960) and Acinetobacter spp. (n=429). The predominant species of EB are shown in figure below. MICs were determined by broth microdilution following CLSI methodology for MEM/NAC at a fixed 1:1 ratio (w:w) and by titrating MEM with a constant concentration of NAC at 4 mg/L. Results were compared with MIC values of MEM and NAC alone and standard of care antibiotics, including ceftazidime/avibactam (CAZ/AVI).

    Results: MIC50/90 for MEM, NAC and MEM/NAC against all EB isolates and by species are shown in the figure below. NAC alone displayed a bimodal MIC distribution for EB, with a prominent separation at ≤4 mg/L. MEM/NAC 1:1 inhibited 99.5, 99.7 and 99.9% of the 3306 EB isolates tested, at ≤2, ≤4 and ≤8 mg/L respectively; while MEM inhibited 96.5, 96.8 and 97.3% of the isolates at the same concentrations. Of 117 (3.5% of total EB) MEM non-susceptible (by EUCAST) and multidrug resistant (MDR, by Magiorakos AP, et al, 2012) EB, 87.2, 92.3 and 96.6% were inhibited by MEM/NAC 1:1 at ≤2, ≤4 and ≤8 mg/L respectively. Additionally, MEM/NAC1:1 displayed MIC ≤8 mg/L for 33 out of 37 CAZ/AVI-resistant MDR EB isolates. MEM/NAC had a similar activity to MEM alone against Pseudomonas spp. and Acinetobacter spp.

     

    Conclusion: MEM/NAC combination shows excellent in vitro activity against current clinical EB isolates and the potential to extend MEM activity to MDR, MEM non-susceptible and CAZ/AVI-resistant isolates, which supports the continued clinical development of MEM/NAC for infections caused by CREs.

    This project has been funded in part under HHS BARDA Contract HHSO100201600038C.

    Rusudan Okujava, PhD1, Fernando Garcia-Alcalde, PhD1, Andreas Haldimann, PhD1, Claudia Zampaloni, PhD1, Ian Morrissey, PhD2, Sophie Magnet, PhD2, Nimmi Kothari, MSc2, Ian Harding, PhD3 and Kenneth Bradley, PhD1, (1)Roche Pharma Research and Early Development, Immunology, Inflammation and Infectious Diseases, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland, (2)IHMA Europe Sàrl, Monthey, Switzerland, (3)Micron Research Ltd, Ely, Cambs, United Kingdom

    Disclosures:

    R. Okujava, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland: Employee , Salary .

    F. Garcia-Alcalde, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland: Employee , Salary .

    A. Haldimann, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland: Employee , Salary .

    C. Zampaloni, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland: Employee , Salary .

    I. Morrissey, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland: Research Contractor , Contracting fee to IHMA .

    S. Magnet, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland: Research Contractor , Contracting fee to IHMA .

    N. Kothari, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland: Research Contractor , Contracting fee to IHMA .

    I. Harding, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland: Research Contractor , Contracting fee to Micron .

    K. Bradley, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland: Employee , Salary .

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