Clinical Outcomes and Costs of Multi-Drug Resistant Gram Negative Bacterial Bloodstream Infections: Initial Results from a 12-year Prospective Cohort Study

Background: The clinical and economic impact of bloodstream infections (BSI) due to multi-drug resistant (MDR) Gram negative bacteria (GNB) are incompletely understood.

Methods: From 2004-2015, all adult inpatients with GNB BSI at Duke Hospital were prospectively enrolled. MDR was defined as resistant to ≥3 antibiotic classes. Infection route was defined as: 1) hospital-acquired, 2) healthcare-associated, community-acquired, or 3) non-healthcare-associated, community-acquired. Clinical outcomes and inpatient costs associated with MDR status were identified.

Results: 1266 unique patients were enrolled.  Of these, 402 (32%) had MDR bacteria. In a multivariable logistic regression, factors associated with MDR infection included history of solid organ or hematological transplant (odds ratio [OR] 1.61; 95% confidence interval [CI] 1.07-2.44; P=0.02) and hospital-acquired infection (OR 1.50; 95% CI 1.13-1.98; P=0.005). Patients with MDR infections were more likely to have longer hospital length of stay [LOS] (Median 11 vs. 8 days; P<0.0001). Unadjusted in-hospital mortality did not significantly differ between the MDR (25.4% [102/402]) and non-MDR (21.3% [184/864]) groups (P=0.10). Unadjusted mean costs were 37% higher in patients with MDR BSI than non-MDR BSI ($156,312 vs. $114,197; P<0.0001), and this persisted after adjustment for patient demographics, APACHE-II scores, infection route, and medical co-morbidities (mean ratio 1.24; 95% CI 1.10- 1.40; P=0.0005) (Figure 1). Statistical significance was not maintained when hospital LOS was added to above covariates (mean ratio 1.06; 95% CI 0.97-1.17; P=0.20). Adjusted analysis of patient sub-populations revealed that the increased cost of MDR infections stemmed from two patient groups: 1) healthcare-associated, community-acquired infections (MDR mean ratio 1.31, 95% CI 1.12-1.54, P=0.0006), and 2) those with severe chronic illnesses (i.e., APACHE-II chronic health score = 5) (MDR mean ratio 1.38, 95% CI 1.20-1.59, P<0.0001).

Conclusion: MDR GNB BSI are associated with longer hospital LOS and increased inpatient costs. MDR infections in chronically ill patients with frequent healthcare contact are driving the increased cost.