Journal Article

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

Fridkin, Scott, Rhee, Chanu, Suffredini, Anthony F, Danner, Robert L, Klompas, Michael, Adjemian, Jennifer, Kadri, Sameer S, Palmore, Tara N, Dekker, John P, Spaulding, Alicen B, Ricotta, Emily, Hooper, David C, Lai, Yi Ling, Powers, John H, Prevots, D Rebecca

2018

Overview

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. Resistance to all first-line agents or difficult-to-treat resistance (DTR) was observed in 1% of gram-negative bacteremias. DTR was identified at half the hospitals; nearly 80% of patients with DTR received \"reserve\" agents. Mortality risk increased with decreasing active first-line categories.

• Publisher: Oxford University Press
• Subject: Adolescent / Adult / Aged / and Commentaries / Anti-Bacterial Agents - therapeutic use / Bacteremia - drug therapy / Bacteremia - epidemiology / Carbapenems - therapeutic use / Databases, Factual / Drug Resistance, Multiple, Bacterial / Editor's Choice / Female / Fluoroquinolones - therapeutic use / Gram-Negative Bacteria - drug effects / Gram-Negative Bacterial Infections - drug therapy / Gram-Negative Bacterial Infections - mortality / Hospitals / Humans / Male / Microbial Sensitivity Tests / Middle Aged / Prevalence / Prognosis / Retrospective Studies / Treatment Outcome / United States - epidemiology / Young Adult