Assessment of Antibiotic Use and Interhospital Variability in Antibiotic Resistant Gram-Negative Pathogens in U.S. Acute Care Hospitals, 2012-2017 Open Access

Duka, Shae (Spring 2021)

Permanent URL: https://etd.library.emory.edu/concern/etds/z603qz68v?locale=en
Published

Abstract

Background: Antibiotic resistance (AR) is a growing threat in the United States, and Gram-negative pathogens such as Carbapenem-resistant Enterobacteriaceae (CRE), Carbapenem-resistant (CR) Acinetobacter spp. and Multi-drug resistant Pseudomonas aeruginosa (MDR P. aeruginosa) have become resistant to nearly all first-line antibiotics. This study assessed drivers of antibiotic-resistant infections by examining interhospital variability, specifically in antibiotic use (AU), of these three pathogens and combined, at the hospital level.

Methods: Clinical microbiology and discharge data from U.S. hospitals in the Premier Healthcare Database from 2012 -2017 were analyzed. The primary exposure, total AU, was measured in days of therapy (DOT) per 1,000 patient days. Rates of antibiotic resistant (AR) infections were measured as the number of specimens that tested resistant (R) to specified antibiotics for each pathogen, per 1,000 discharges. AU and AR were reported descriptively by year, and the unadjusted relationship was examined through scatterplots. Twelve Poisson regression models assessed the association between total AU and AR infection rates of each pathogen and type (all, hospital-onset (HO), community-onset (CO)), adjusting for hospital characteristics and covariates.

Results: Unadjusted results showed very low combined infection rates (all pathogens of interest) across all years (median hospital level rate=1.68 per 1,000 discharges). MDR P. aeruginosa had the highest median hospital-level rate of 1.17, followed by CRE (median=0.22) and CR Acinetobacter spp. (median=0.07). Scatterplots of unadjusted total AU and unadjusted AR rates showed no relationship between pathogens, except for CR Acinetobacter spp. which displayed a weak but positive linear relationship. In the adjusted models, no association was found between total AU and AR infection rates except for the CR Acinetobacter spp. models where AU was significantly associated with each type (all, HO, CO) (IRR=1.06, 1.12, 1.04, respectively). Significant associations between urban/rural status and census divisions (specifically the Middle Atlantic, East North Central and East South Central) appeared frequently across models.

Conclusion: These findings suggest variability in AR may be associated with total antibiotic use in CR Acinetobacter spp.; however, future studies should examine antibiotic class-specific associations. Additionally, significant associations between AR infection rates and urban/rural status and census divisions were found – highlighting focus areas for future research. 

Table of Contents

Introduction ...............................................................................................................1 Methods.....................................................................................................................13

Study Design, Population, and Data Source ...................................................................13

Exposure, Outcomes, and Covariates ............................................................................13

Analytic Methods........................................................................................................16

Objective One .............................................................................................................16

Objective Two..............................................................................................................16

Ethics Approval ...........................................................................................................18

Results .......................................................................................................................19

Characteristics of Hospitals ..........................................................................................19

Unadjusted Rates of Antibiotic Resistant Infections ........................................................19

Antibiotic Use ..............................................................................................................21

Association Between Antibiotic Use and Antibiotic Resistant Infection Rates ....................22

Discussion ....................................................................................................................28

Limitations ...................................................................................................................31

Strengths ......................................................................................................................31

Future Directions ..........................................................................................................32

References ....................................................................................................................33

Tables ...........................................................................................................................38 Figures...........................................................................................................................49 

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