Format

Send to

Choose Destination
Clin Infect Dis. 2018 Nov 28;67(12):1803-1814. doi: 10.1093/cid/ciy378.

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.

Author information

1
Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, Maryland.
2
Division of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School, Boston.
3
Epidemiology Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda.
4
United States Public Health Service, Commissioned Corps, Rockville.
5
National Institutes of Health Clinical Center, Bethesda, Maryland.
6
Department of Medicine, Brigham and Women's Hospital.
7
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts.
8
Department of Laboratory Medicine, National Institutes of Health Clinical Center, Bethesda.
9
Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., NCI Campus at Frederick, Maryland.
10
Division of Healthcare Quality and Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.

Abstract

Background:

Resistance to all first-line antibiotics necessitates the use of less effective or more toxic "reserve" agents. Gram-negative bloodstream infections (GNBSIs) harboring such difficult-to-treat resistance (DTR) may have higher mortality than phenotypes that allow for ≥1 active first-line antibiotic.

Methods:

The Premier Database was analyzed for inpatients with select GNBSIs. DTR was defined as intermediate/resistant in vitro to all ß-lactam categories, including carbapenems and fluoroquinolones. Prevalence and aminoglycoside resistance of DTR episodes were compared with carbapenem-resistant, extended-spectrum cephalosporin-resistant, and fluoroquinolone-resistant episodes using CDC definitions. Predictors of DTR were identified. The adjusted relative risk (aRR) of mortality was examined for DTR, CDC-defined phenotypes susceptible to ≥1 first-line agent, and graded loss of active categories.

Results:

Between 2009-2013, 471 (1%) of 45011 GNBSI episodes at 92 (53.2%) of 173 hospitals exhibited DTR, ranging from 0.04% for Escherichia coli to 18.4% for Acinetobacter baumannii. Among patients with DTR, 79% received parenteral aminoglycosides, tigecycline, or colistin/polymyxin-B; resistance to all aminoglycosides occurred in 33%. Predictors of DTR included urban healthcare and higher baseline illness. Crude mortality for GNBSIs with DTR was 43%; aRR was higher for DTR than for carbapenem-resistant (1.2; 95% confidence interval, 1.0-1.4; P = .02), extended-spectrum cephalosporin-resistant (1.2; 1.1-1.4; P = .001), or fluoroquinolone-resistant (1.2; 1.0-1.4; P = .008) infections. The mortality aRR increased 20% per graded loss of active first-line categories, from 3-5 to 1-2 to 0.

Conclusion:

Nonsusceptibility to first-line antibiotics is associated with decreased survival in GNBSIs. DTR is a simple bedside prognostic measure of treatment-limiting coresistance.

PMID:
30052813
PMCID:
PMC6260171
[Available on 2019-11-28]
DOI:
10.1093/cid/ciy378

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center