New Designation for Some Gram-Negative Bacteremia Increases Treatment Options

Nonsusceptibility to first-line antibiotics is associated with decreased survival in gram-negative bloodstream infections.

New research published in Clinical Infectious Diseases concluded that nonsusceptibility to multiple first-line antibiotics is associated with increased mortality in gram-negative bloodstream infections.

Investigators used the Premier Healthcare Database to identify inpatients with select gram-negative bloodstream infections, assigned the designation of difficult-to-treat resistance (DTR), and identified predictors of this new status. Investigators defined DTR as intermediate or resistant in vitro to all ß-lactam categories, including carbapenems and fluoroquinolones.

From 2009 to 2013, 1% of the 45,011 identified infections exhibited DTR, with ranges from 0.04% for Escherichia coli to 18.4% for Acinetobacter baumannii. Among the patients with DTR, 79% received parenteral aminoglycosides, tigecycline, or colistin/polymyxin-B and 33% were resistant to all aminoglycosides. The predictors of DTR included urban healthcare and higher baseline illness. Crude mortality for DTR was 43%, whereas the adjusted relative risk of mortality was higher for DTR than for carbapenem-resistant (1.2; 95% CI 1.0-1.4; P =.02), extended-spectrum cephalosporin-resistant (1.2; 95% CI, 1.1-1.4; P =.001), or fluoroquinolone-resistant (1.2; 95% CI, 1.0-1.4; P =.008) infections. The adjusted relative risk for mortality increased 20% per graded loss of active first-line categories, going from 3 to 5, to 1 to 2, to 0.

The investigators did note several study limitations. The cohort of hospital patients selected may not be nationally representative. Strain virulence, adequacy of source control, or encounter-level diagnostic codes for source of bacteremia could not be evaluated, meaning the true source may not be represented. Certain confounding variables, such as severity of illness, could not be accounted for, and conclusions on long-term outcomes or the generalizability of the estimates to non-US regions are unavailable. Reporting on trends in DTR resulting from break point changes and “their piecemeal implementation at different hospitals” was not possible. Testing practices varied across hospitals, which may bias the classification system, and although DTR classification can be applied to other pathogens, the scheme requires frequent updating as new antibiotics and resistance patterns emerge. However, the strength of DTR and its accurate reflection of the effect of bacterial resistance on bedside decisions on antibiotic treatments cannot be overlooked; DTR provides an avenue to fill the gap left by global designations (such as multidrug-resistant and extensively drug-resistant ) in accounting for the efficacy and safety of available options of antibiotics.

The results, according to the investigators, demonstrate that “DTR is a novel classifier of antimicrobial coresistance that integrates the impact of resistance on antibiotic choices and the effect of these choices on clinical outcome.” Further, the investigators concluded, “DTR more fully encompasses key aspects of antimicrobial resistance that affect mortality risk.”

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Kadri SS, Adjemian J, Lai YL, et al. Difficult-to-treat resistance in gram-negative bacteremia at 173 US hospitals: Retrospective cohort analysis of prevalence, predictors, and outcome of resistance to all first-line agents [published online July 23, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy378