2377. Difficult to Treat Resistance (DTR) - A Novel Antimicrobial Resistance Classifier that Reliably Predicts Outcome in Gram-negative Bloodstream Infections
Session: Oral Abstract Session: Epidemiology and Outcomes of Resistant Gram-Negative Organisms
Saturday, October 29, 2016: 3:00 PM
Room: 388-390

Background: Difficult to treat Resistance (DTR) is defined as the treatment-limiting burden of resistance to high-efficacy, low-toxicity (HELT) antibiotics (penicillins, cephalosporins, carbapenems, quinolones; Table 1). Patients with gram-negative bloodstream isolates (GNBSI) exhibiting DTR are more likely to receive ineffective empiric therapy, and thereby suffer worse outcomes. However, the impact of graded levels of DTR on mortality has not been investigated.

Methods: Unique inpatient encounters from 2009-13 with ³1 GNBSI in the PremierTM database were categorized into non-DTR, DTR-2, DTR-1 and full DTR (for >2, 2, 1 and 0 active HELT agents). Multivariable logistic regression was performed to determine the adjusted odds ratio (aOR) and 95% confidence interval (CI) of in-hospital mortality for patients with GNBSI by level of DTR. Mortality was adjusted for patient- (age, gender, Elixhauser comorbidity index and ICU stay), GNBSI- (species, source, hospital onset and year) as well as hospital-level characteristics.

Results: Of 43,164 unique patients with GNBSIs, we detected 1,285 (3%) with DTR-2, 927 (2%) with DTR-1 and 415 (1%) with full DTR. GNBSI mortality increased with rising DTR strata, from 15% for non-DTR to 43% for full DTR; this trend was true for all species evaluated (Figure 1). The stepwise increase in mortality with successive levels of DTR persisted on multivariable analysis; 20% for patients with DTR-2 (aOR=1.2, 95% CI=1.0-1.4; p=0.02), 40% for DTR-1 (aOR=1.4, 95% CI=1.2-1.7; p<0.0001) and 90% for full DTR (aOR=1.9, 95% CI=1.5-2.4; p<0.0001) compared to non-DTR GNBSIs (Table 2). Age, Elixhauser index, ICU stay, species, source, hospital onset of GNBSI, hospital region, urbanicity, teaching status, and DTR status were independent predictors of death (p<0.05 for all).

Conclusion: DTR is independently associated with increased risk of death in patients with GNBSI. Risk escalates substantially as the number of active HELT agents diminishes to zero. By factoring in the efficacy and toxicity of available antibiotics, the DTR classifier can be used to determine the impact of antimicrobial resistance on outcome.

Sameer S. Kadri, MD, MS.1, Alicen B. Spaulding, PhD, MPH2, Yi Ling Lai, MPH2, D. Rebecca Prevots, PhD, MPH3, John P. Dekker, M.D., Ph.D.4, Tara N. Palmore, MD5, Chanu Rhee, MD, MPH6, Michael Klompas, MD, MPH, FRCPC, FIDSA7, David C. Hooper, MD8, Scott Fridkin, MD, FIDSA9, Robert L. Danner, MD10 and Jennifer Adjemian, PhD11, (1)Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, MD, (2)NIH/NIAID, Bethesda, MD, (3)Epidemiology Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD, (4)Department of Laboratory Medicine, NIH Clinical Center, NIH, Bethesda, MD, (5)National Institutes of Health Clinical Center, Bethesda, MD, (6)Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, (7)Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, (8)Harvard Medical School and Massachusetts General Hospital, Boston, MA, (9)Division of Healthcare Quality and Promotion, Centers for Disease Control and Prevention, Atlanta, GA, (10)Critical Care Medicine, National Institutes of Health, Bethesda, MD, (11)NIH/NIAD, Bethesda, MD


S. S. Kadri, None

A. B. Spaulding, None

Y. L. Lai, None

D. R. Prevots, None

J. P. Dekker, None

T. N. Palmore, None

C. Rhee, None

M. Klompas, None

D. C. Hooper, None

S. Fridkin, None

R. L. Danner, None

J. Adjemian, None

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