357. Optimized Beta-Lactam Therapy Improves Survival in Carbapenem Non-Susceptible Gram-Negative Infections
Session: Poster Abstract Session: HAI: MDRO-GNR/Emerging Resistant Bacterial Pathogens
Thursday, October 5, 2017
Room: Poster Hall CD
  • FlyntL_IDWeek2017_BlactamOptimization.pdf (457.9 kB)
  • Background: Infections due to carbapenem non-susceptible organisms are associated with significant mortality. The objective of this study was to identify modifiable predictors for survival in patients with these infections with a focus on antimicrobial therapies.

    Methods: This was a case-control study at a four-hospital health-system. Patients were evaluated for inclusion if they were ≥ 18 years with an infection due to a carbapenem non-susceptible organism from 11/2013 to 10/2016. Exclusion criteria were infections localized to the urinary tract or hospice designation. The primary objective was to identify independent predictors of all cause 30-day mortality. Pharmacodynamic (PD) optimized BL therapy was the exposure of interest, defined as doses administered to patients expected to obtain an estimated target attainment of ≥ ~90% of fT>MIC targets associated with a 1 log kill for the isolated pathogens MIC, based on published PK/PD literature and the renal function of the patient.

    Results: 203 patients were included. Median age was 61 (49-70) and charlson comorbidity index was 2 (1-4). 41 (20%) had septic shock and 30-day mortality was observed in 63 (31%). P. aeruginosawas the causative pathogen in 149 (73%) of patients with Enterobacteriaceae representing the other 54 (27%). Lower respiratory tract infection were the most common (n = 128; 63%). Fifty-five patients received combination therapy (27%) with the most common combination consisting of BL and aminoglycoside (38%). Mortality was observed in 22% of patients receiving combination therapy compared to 35% monotherapy (p = 0.07). 45% of patients received a PD optimized BL, 25% received a BL not PD optimized, and 30% without a BL. Receipt of PD optimized BL and combination therapy were independent predictors of survival (table).

    Conclusion: PD optimized BL and combination therapy were associated with improved 30 day survival.




    n = 140


    n = 63

    Crude OR (95% CI)

    Adjusted OR (95% CI)

    Received PD optimized Beta-lactam

    71 (78%)

    20 (22%)

    2.2 [1.2-4.1]

    2.2 [1.1-4.3]

    Septic Shock

    16 (39%)

    25 (61%)

    0.2 [0.1-0.4]

    0.1 [0.1-0.3]

    Combination Therapy

    44 (80%)

    11 (20%)

    1.9 [1-4.6]

    3.0 [1.3-7.2]


    18 (53%)

    16 (47%)

    0.4 [0.2-0.9]

    0.4 [0.2-0.8]

    Lauren K Flynt, PharmD, Pharmacy, Henry Ford Hospital, Detroit, MI, Rachel M Kenney, PharmD, Henry Ford Hospital, Detroit, MI, Michael Veve, PharmD, Wayne State University College of Pharmacy, Detroit, MI, Jason Pogue, PharmD, Detroit Medical Center/Wayne State University, Detroit, MI, Odaliz Abreu-Lanfranco, MD, Infectious Diseases, Henry Ford Health System, Detroit, MI and Susan L Davis, PharmD, Pharmacy Practice, Wayne State University, Detroit, MI


    L. K. Flynt, None

    R. M. Kenney, None

    M. Veve, None

    J. Pogue, None

    O. Abreu-Lanfranco, None

    S. L. Davis, Allergan: Grant Investigator and Scientific Advisor , Consulting fee and Research grant
    Merck: Grant Investigator and Scientific Advisor , Consulting fee and Research grant

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 4th with the exception of research findings presented at the IDWeek press conferences.