1391. Influence of MIC in Clinical Outcomes of Enterococcus faecium Bacteremia Treated with Daptomycin: Is It Time to Change the Breakpoint?
Session: Oral Abstract Session: Resistance Mechanisms
Saturday, October 10, 2015: 10:45 AM
Room: 25--ABC
Background: Daptomycin (DAP) has become a key front-line antibiotic for E. faecium (Efm) bloodstream infections (BSI). We previously showed that Efm strains with DAP MICs in the higher end of susceptibility (MIC 3-4 µg/mL, breakpoint 4 µg/mL) frequently harbor mutations in genes associated with DAP-R, compromising DAP bactericidal activity in vitro. Our hypothesis was that patients with Efm BSI exhibiting DAP MICs 3-4 µg/mL treated with DAP were more likely to have worse outcomes than those exhibiting DAP MICs ≤2 µg/mL.

Methods: We conducted a multicenter (n=3) retrospective cohort study from 2010-15 including patients with Efm BSI for whom the following criteria were met: i) availability of initial isolates, ii) follow-up blood culture within 7 days, and iii) ≥72 hours of DAP therapy. Exclusions included age<18, pregnancy, and a DAP-R initial isolate. All DAP MICs were determined in the same laboratory by E-test method in a blinded fashion. Relevant clinical and demographic data were collected for univariate and multivariate regression analysis. The primary outcome was microbiologic failure, defined as clearance of bacteremia >4 days, with secondary outcome as in-hospital mortality.

Results: A total of 56 patients met the inclusion criteria and 29 (52%) were infected with isolates exhibiting DAP MICs 3-4 µg/mL. A total of 31 (55%) patients had microbiologic failure and 23 patients (41%) died during hospital admission. Microbiologic failure occurred more often in patients with Efm BSI exhibiting MICs of 3-4 µg/mL (72% versus 37%, p=0.008). Charlson score >4, immunosuppression, and MIC 3-4 µg/mL were independently associated with prolonged time to clearance. After logistic regression analysis, only immunosuppression and DAP MIC 3-4 µg/mL remained significant, with internal validation using bootstrap analysis (p<0.05). Variables associated with in-hospital mortality were liver disease, ICU stay and acute kidney injury.

Conclusion: In patients with Efm BSI treated with DAP, the presence of DAP MICs of 3-4 µg/mL in the initial isolate was significantly associated with microbiologic failure in patients receiving DAP therapy. Our data further confirms previous in vitro observations and strongly suggests that a change in the DAP breakpoint should be considered.

Bhavarth Shukla, MD, MPH1,2, Samuel Shelburne, MD, PhD3, Katherine Reyes, MD, MPH4, Jessica Lewis, MD5, Sandra Rincon, MSc6, Diana Panesso, PhD6, Javier Adachi, MD, FIDSA7, Costi D. Sifri, MD, FIDSA8, Marcus Zervos, MD, FIDSA4, Jose Munita, MD9, Rodrigo Hasbun, MD, MPH10 and Cesar Arias, MD, PhD, FIDSA9, (1)Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, (2)Division of Infectious Diseases, University of Texas Medical School at Houston, Houston, TX, (3)Infectious Disease, The University of Texas MD Anderson Cancer Center, Houston, TX, (4)Division of Infectious Diseases, Henry Ford Hospital, Detroit, MI, (5)Division of Infectious Diseases and International Health, University of Virginia Health System, Charlottesville, VA, (6)Universidad El Bosque, Bogota, Colombia, (7)Dept. of Infectious Diseases, Infection Control and Employee Health, The University of Texas - MD Anderson Cancer Center, Houston, TX, (8)Department of Medicine, Division of Infectious Diseases and International Health, Hospital Epidemiology/Infection Prevention and Control, University of Virginia Health System, Charlottesville, VA, (9)University of Texas Medical School at Houston, Houston, TX, (10)Infectious Diseases, University of Texas Health, Houston, TX

Disclosures:

B. Shukla, None

S. Shelburne, None

K. Reyes, None

J. Lewis, None

S. Rincon, None

D. Panesso, None

J. Adachi, Cubist (Merck): Grant Investigator , Research grant

C. D. Sifri, None

M. Zervos, Pfizer: Investigator , Research grant to Henry Ford Hospital
Cerexa: Investigator , Research grant to Henry Ford Hospital
Tetraphase: Investigator , Research grant to Henry Ford Hospital
Cubist: Investigator , Research grant to Henry Ford Hospital
Forest Research Institute: Investigator , Research grant to Henry Ford Hospital
AstraZeneca: Investigator , Research grant
Cempra: Investigator , Research grant
Durata Therapeutics: Investigator , Research grant

J. Munita, None

R. Hasbun, Medicine''s Company: Speaker's Bureau , Speaker honorarium
Cubist: Speaker's Bureau , Speaker honorarium
Theravance: Speaker's Bureau , Speaker honorarium
Pfizer: Speaker's Bureau , Speaker honorarium

C. Arias, Pfizer: Grant Investigator and Speaker's Bureau , Grant recipient and Speaker honorarium
Merck Sharp and Dohme: Grant Investigator and Speaker's Bureau , Grant recipient and Speaker honorarium
Cubist: Grant Investigator and Speaker's Bureau , Grant recipient and Speaker honorarium
Theravance: Grant Investigator and Speaker's Bureau , Grant recipient and Speaker honorarium
Bayer: Consultant , Consulting fee

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