1839. Activity of Imipenem-Relebactam (MK-7655) Against Enterobacteriaceae and Pseudomonas aeruginosa from Respiratory Tract Infections in North America - SMART 2015
Session: Poster Abstract Session: Antibacterial Susceptibility Surveillance
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • Merck_P05_IMI REL RTI NA_IDSA 2016_v01_final.pdf (812.0 kB)
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    Background: Relebactam (formerly MK-7655) (REL) is a newly developed beta-lactamase inhibitor of class A and class C carbapenemases.  REL restores the in vitro activity of imipenem (IMI) against Enterobacteriaceae, including those producing KPC, and Pseudomonas aeruginosa (PA). In this study we evaluated the ability of REL to restore IMI susceptibility to a collection of gram-negative isolates from respiratory tract infections (RTI) from North America collected as part of the 2015 SMART surveillance program.

    Methods: 26 hospitals in the US (19) and Canada (7) collected up to 50 consecutive gram-negative pathogens from RTIs.  MICs were determined for 96 PA and 981 non-Proteae Enterobacteriaceae (NPE) using CLSI broth microdilution. Proteae were excluded due to intrinsic non-susceptibility to IMI. REL was tested at a fixed concentration of 4 µg/mL in combination with IMI.  The percent susceptible (S) was assessed using CLSI breakpoints.  IMI S breakpoints of ≤1 µg/mL (NPE) and ≤2 µg/mL (PA) were applied to IMI/REL.  

    Results:  The cumulative percent of isolates at each IMI and IMI/REL MIC is shown in the table.

    Organism

    N

    Drug

    MIC (µg/mL)

     

     

     

    ≤0.5

    1

    2

    4

    8

    16

    32

    >32

    P. aeruginosa

    769

    IMI

    21.8

    56.6

    68.7

    73.9

    82.4

    93.9

    99.5

    100

    P. aeruginosa

     

    IMI/REL

    71.4

    82.7

    92.2

    96

    98.4

    99.6

    99.7

    100

    P. aeruginosa, IMI NS

    241

    IMI

     

     

     

    16.6

    44.0

    80.5

    98.3

    100

    P. aeruginosa, IMI NS

     

    IMI/REL

    14.5

    45.2

    75.1

    87.1

    95.0

    98.8

    99.2

    100

    NPE

    1060

    IMI

    82.6

    92.3

    97.5

    98.3

    98.8

    99.3

    99.6

    100

    NPE

     

    IMI/REL

    90.9

    97.7

    99.6

    100

     

     

     

     

    NPE, IMI NS

    82

    IMI

     

     

    67.1

    78

    84.1

    91.5

    95.1

    100

    NPE, IMI NS

     

    IMI/REL

    26.8

    70.7

    95.1

    100

     

     

     

     

    Shaded area indicates susceptible by CLSI 2016 imipenem breakpoint; MIC90 bolded; NPE, non-Proteae Enterobacteriaceae; IMI, imipenem; REL, relebactam; NS, non-susceptible

    Among 769 PA, 69% (528) were S to IMI; of the 241 non-susceptible (NS) isolates, 181 (75%) were rendered S by the addition of REL, for a final 92% S. Among 1,060 NPE, 92% (978) were S to IMI; of the 82 NS isolates, 58 (71%) were rendered S by the addition of REL, for a final 98% S. 

    Conclusion: Relebactam exhibited strong potential for restoring the in vitro activity of IMI against many RTI pathogens otherwise NS to carbapenems.  Further development of this compound could provide a valuable therapeutic option for treating infections caused by resistant gram-negative bacilli.

     

    Meredith Hackel, PhD, MPH1, Katherine Young, MS2, Mary Motyl, PhD3 and Dan Sahm, PhD1, (1)International Health Management Associates, Inc., Schaumburg, IL, (2)Merck & Co., Inc., Kenilworth, NJ, (3)Infectious Disease, Merck & Co., Inc., Kenilworth, NJ

    Disclosures:

    M. Hackel, IHMA, Inc.: Independent Contractor , Research support

    K. Young, Merck & Co., Inc.: Employee , Salary

    M. Motyl, Merck & Co., Inc.: Employee , Salary

    D. Sahm, IHMA, Inc.: Independent Contractor , Research support

    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.