119. Previous Daptomycin Exposure Predicts Daptomycin Non-Susceptible Enterococcus faecium Bloodstream Infections in Adult Leukemia Patients
Session: Oral Abstract Session: Coming Soon to a Bloodstream Near You
Thursday, October 27, 2016: 11:45 AM
Room: 275-277
Background:

Daptomycin (DAP) is frequently used off-label to manage vancomycin-resistant Enterococcus faecium (VRE) bloodstream infections (BSI) in cancer patients, however the emergence of DAP non-susceptible E. faecium (DNSEf) strains threatens its clinical utility. There are limited data regarding risk factors for the development of BSI due to DNSEf. The purpose of this study was to assess prior DAP exposure as a risk factor for DNSEf BSI in leukemia patients.

Methods:

This was a retrospective cohort study of all adult (age ≥ 18 years) leukemia patients with a first episode of E. faecium BSI at The University of Texas MD Anderson Cancer Center from 6/2013 to 7/2015. DAP non-susceptibility was defined as a minimum inhibitory concentration (MIC) of >4 mg/L by Etest. Previous antibiotic exposure and microbiologic data were correlated to DNSEf. Classification and Regression Tree (CART) analysis was used to identify the most significant DAP exposure / DNSEf breakpoint.

Results:

A total of 77 patients (mean age 51 ± 15 years; 64% male) with E. faecium BSI and DAP susceptibility information were identified. Of these, 62% had acute myeloid leukemia, 80% were receiving salvage chemotherapy, and 83% had an absolute neutrophil count (ANC) < 500 cells/mm3. DAP non-susceptibility was reported in 17 (22%) of the isolates, whereas resistance to vancomycin and linezolid was found in 69% and 17%, respectively. Resistance to all 3 antibiotics was found in 5% of the cases. Compared to those with DAP-susceptible isolates, more patients with DNSEf BSI had received at least one dose of DAP in the 90 days prior to the onset of BSI (88% vs. 43%, p < 0.01). CART analysis identified the receipt of > 13 days of DAP in the preceding 90 days as a significant risk factor for DNSEf (67% vs. 11%; RR 5.90 [95% CI 2.70–12.93], p < 0.01; ROC 0.753). No other antibiotic exposures were found to correlate with DNSEf.

Conclusion:

Prior exposure to DAP (> 13 days) was associated with a nearly 6-fold increased risk of developing DNSEf BSI. These findings establish the importance of taking into account previous DAP exposure as a decision tool for choosing empiric antimicrobial therapy in patients with E. faecium BSI and suggest that antimicrobial stewardship efforts may be critical in preventing the emergence of DNSEf BSI.

Adam J. Dipippo, PharmD1, Frank P. Tverdek, PharmD1, Jeffrey J. Tarrand, MD, MS2, Jose M. Munita, MD3,4, Cesar Arias, MD, PhD, FIDSA3,4, Samuel a. Shelburne, MD, PhD3, Truc T. Tran, PharmD4,5 and Samuel L. Aitken, PharmD1, (1)Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX, (2)Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, (3)Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, (4)Department of Internal Medicine, University of Texas McGovern Medical School at Houston, Houston, TX, (5)Department of Pharmacy Services, Memorial Hermann Hospital - Texas Medical Center, Houston, TX

Disclosures:

A. J. Dipippo, None

F. P. Tverdek, Astellas: Scientific Advisor , Consulting fee

J. J. Tarrand, None

J. M. Munita, None

C. Arias, None

S. A. Shelburne, None

T. T. Tran, None

S. L. Aitken, Merck: Speaker's Bureau , Speaker honorarium
Theravance: Scientific Advisor , Consulting fee
Actavis: Scientific Advisor , Consulting fee

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