1358. In vitro activity of ceftazidime-avibactam and comparator agents against Pseudomonas aeruginosa causing intra-abdominal, lower respiratory, and urinary tract infections collected in Latin America as part of the INFORM global surveillance program, 2012-2016
Session: Poster Abstract Session: Novel Agents
Friday, October 5, 2018
Room: S Poster Hall
Posters
  • Pfizer_P79_CazAvi_IDSA 2018_FINAL.pdf (253.2 kB)
  • Background: The non-β-lactam β-lactamase inhibitor avibactam (AVI) is active against class A, C and some class D β-lactamases, in combination with ceftazidime (CAZ) has been approved by the FDA and EMA for treatment of intra-abdominal infections (IAI), lower respiratory tract infections (LRTI) and urinary tract infections (UTI).  This study reports on the in vitro activity of (CAZ-AVI) and comparators versus P. aeruginosa (Paer) collected from IAIs, LRTIs and UTIs in Latin America as part of the INFORM surveillance study from 2012-2016.

    Methods: For INFORM surveillance over 2012-2016 in Latin America, 1595 non-duplicate Paer isolates linked to IAIs, LRTIs and UTIs were collected from 26 clinical sites in 6 countries. Susceptibility testing was done using broth microdilution according to CLSI guidelines and using CLSI 2018 breakpoints. CAZ was tested with AVI at a fixed concentration of 4 mg/ml. Meropenem (MEM) non-susceptible organisms were screened for β-lactamase genes by PCR.

    Results: Among the full collection of Paer, CAZ-AVI showed consistently higher % susceptibilities than all comparators except for colistin (CST) for all infection sources. The addition of AVI to CAZ resulted in an increase in susceptibility ranging from 14.2% (IAI) to 19.5% (UTI). Against the non-metallo-β-lactamase (MBL) harboring subset, CAZ-AVI showed extremely potent activity (MIC90, 8 mg/ml) for all infection sources. In this subset, the activity of CAZ-AVI approached that of colistin for IAIs (susceptibility of 93.3% vs. 96.4%, respectively).

    Organism/Phenotype/Infection source (n)

    Drug (MIC90 [µg/ml]/% Susceptible)

    CAZ-AVI

    CAZ

    MEM

    CST

    P aeruginosa, All sources (1595) a

    16

    86.0

    64

    68.7

    > 8

    61.9

    2

    96.2

    IAI (295)

    32

    85.1

    64

    70.9

    > 8

    62.4

    2

    96.7

    LRTI (942)

    16

    86.8

    128

    69.3

    > 8

    60.7

    2

    96.3

    UTI (358)

    32

    84.6

    64

    65.1

    > 8

    64.8

    2

    95.8

    P aeruginosa MBL-negative, All sources (1488) b

    8

    91.9

    64

    73.5

    > 8

    66.1

    2

    96.1

    IAI (269)

    8

    93.3

    64

    77.7

    > 8

    68.0

    2

    96.4

    LRTI (889)

    8

    91.8

    64

    73.3

    > 8

    64.0

    2

    96.0

    UTI (330)

    8

    91.2

    64

    70.3

    > 8

    70.3

    2

    96.2

    % susceptible defined using CLSI 2018 breakpoints.

    a CST not tested in 2012 or 2013; Totals for IAI, n=215; LRTI, n=721; UTI, n=286.

    b CST not tested in 2012 or 2013; Totals for IAI, n=196; LRTI, n=677; UTI, n=260.

    Conclusion: CAZ-AVI demonstrated very good in vitro activity against Paer isolates, especially those without MBLs. More isolates were susceptible to CAZ-AVI than to MEM for all infection types.

    Mark Wise, Ph.D1, Krystyna Kazmierczak, Ph.D1, Gregory G. Stone, Ph.D.2 and Dan Sahm, PhD3, (1)IHMA, Inc., Schaumburg, IL, (2)Pfizer, Inc., New York, NY, (3)International Health Management Associates, Inc., Schaumburg, IL

    Disclosures:

    M. Wise, Pfizer Inc.: Consultant , Consulting fee . IHMA, Inc.: Employee , Salary .

    K. Kazmierczak, Pfizer Inc.: Consultant , Consulting fee . IHMA, Inc.: Employee , Salary .

    G. G. Stone, Pfizer Inc.: Employee , Salary . AstraZeneca: Former Employee and Shareholder , Salary .

    D. Sahm, Pfizer Inc.: Consultant , Consulting fee . IHMA, Inc.: Employee , Salary .

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