1838. Activity of Imipenem-Relebactam (MK-7655) Against Enterobacteriaceae and Pseudomonas aeruginosa from Intraabdominal Infections in North America - SMART 2015
Session: Poster Abstract Session: Antibacterial Susceptibility Surveillance
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • Merck_P06_IMI REL IAI NA_IDSA 2016_v01_final.pdf (811.7 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 intraabdominal infections (IAI) 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 100 consecutive gram-negative pathogens from IAI.  MICs were determined for 189 PA and 1,607 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

    189

    IMI

    16.4

    70.4

    78.8

    81

    87.3

    96.3

    99.5

    100

    P. aeruginosa

     

    IMI/REL

    79.9

    89.4

    95.8

    98.4

    100

     

     

     

    P. aeruginosa, IMI NS

    40

    IMI

     

     

     

    10.0

    40.0

    82.5

    97.5

    100

    P. aeruginosa, IMI NS

     

    IMI/REL

    12.5

    50.0

    80.0

    92.5

    100

     

     

     

    NPE

    1607

    IMI

    92.2

    97.9

    98.7

    99.3

    99.6

    99.6

    99.9

    100

    NPE

     

    IMI/REL

    97.5

    99.4

    99.8

    99.9

     

     

     

    100

    NPE, IMI NS

    34

    IMI

     

     

    38.2

    67.6

    79.4

    82.4

    94.1

    100

    NPE, IMI NS

     

    IMI/REL

    44.1

    70.6

    88.2

    97.1

    0

    0

    0

    100

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

    Among 189 PA, 78% (149) were S to IMI; of the 40 non-susceptible (NS) isolates, 32 (80%) were rendered S by the addition of REL, for a final 96% S. Among 1,607 NPE, 98% (1,573) were S to IMI; of the 34 NS isolates, 24 (71%) were rendered S by the addition of REL, for a final 99% S. 

    Conclusion: Relebactam exhibited strong potential for restoring the in vitro activity of IMI against many IAI 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.