Impact of Difficult-to-Treat Resistance in Gram-negative Bacteremia on Mortality: Retrospective Analysis of Nationwide Surveillance Data

Abstract Background Clinically relevant categorization of antimicrobial resistance is critical to mitigating the threat it poses. Difficult-to-treat resistance (DTR) is a recently proposed category defined as nonsusceptibility to all first-line antibiotic agents. Methods A retrospective study was conducted with nonduplicate cases of gram-negative bloodstream infection (GNBSI) caused by 4 major taxa (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter species) identified from a nationwide surveillance database. DTR was defined as nonsusceptibility to all the β-lactams and fluoroquinolones tested. Patient characteristics and mortality were compared between DTR GNBSI and GNBSI caused by carbapenem-resistant but not DTR and extended-spectrum cephalosporin–resistant but not DTR isolates using Centers for Disease Control and Prevention definitions. Adjusted odds ratios (aORs) for 30-day in-hospital mortality were examined for DTR in overall and in propensity score–matched cohorts. Results A total of 1167 episodes of monomicrobial GNBSI were identified, and 147 (12.6%) of the isolates were DTR. The majority of DTR isolates were Acinetobacter species (79.6%) and P. aeruginosa (17.7%). DTR infections were associated with previous antibiotic use, healthcare contact, ventilator use, and lower respiratory tract infection. Crude mortality for GNBSI caused by DTR was 50.3%. A multivariable model showed that only DTR, but not other categories, was significantly associated with mortality (adjusted odds ratio [aOR], 3.58 [95% confidence interval {CI}, 1.27–10.19]). DTR was also a significant predictor for mortality in the analysis of propensity score–matched cohorts (aOR, 3.48 [95% CI, 1.82–6.79]). Conclusions In patients with GNBSI, DTR was associated with higher mortality than those in other resistance categories. Our findings suggest that DTR could be useful for surveillance and prognostication. In this retrospective analysis of nationwide surveillance data, bloodstream infections caused by gram-negative bacteria resistant to all β-lactams and fluoroquinolones (difficult-to-treat resistance) were associated with an increased risk of 30-day in-hospital mortality.