Risk Factors for Mortality in Carbapenem-resistant Enterobacterales in Georgia, 2011 – 2020 Público
Witt, Lucy (Spring 2023)
Abstract
Background
Carbapenem-resistant Enterobacterales (CRE) are an urgent public health threat. Although the high mortality from CRE is well described, modifiable risk factors for mortality, such as possession of an indwelling medical device, have not yet been consistently identified. Furthermore, prior studies have disagreed on the impact carbapenemase enzymes have on mortality.
Methods
Using data from the Georgia Emerging Infections Program, we created a cohort of patients with sterile-site CRE infections between 2012 – 2019. We described the incidence of infection and demographics of the patients. Using log-binomial multivariable modeling, we investigated whether having an indwelling medical device was associated with an increased risk of 90-day mortality when controlling for confounders.
A second, adjacent cohort consisted of isolates from CRE infections (both sterile-site and urine) between 2011 – 2020 for which whole genome sequencing (WGS) was available. Using this data we described the frequency of carbapenemase genes (CP) and evaluated whether having a CP was associated with 90-day mortality when controlling for confounders. We completed time-to-event analyses using a Kaplan Meier analysis and a Cox proportional hazards modeling.
Results
There were 154 patients with sterile-site CRE infections between 2012– 2019. Having an indwelling medical device was not associated with increased mortality (adjusted risk ratio [aRR] 1.29, 95% Confidence Interval [CI] 0.57 – 2.81), however having at least two devices was (aRR 2.00, 95% CI 1.18 – 3.38). For isolates from both sterile-site and urine CRE infections with WGS available (n=284), CPs were not associated with increased 90-day mortality compared to infections with isolates without CPs (aRR 0.92, 95% CI 0.62 – 1.34). Cox proportional hazard modeling found no relationship between survival and CP gene possession (adjusted hazard ratio 1.23, 95% CI 0.75 – 2.01).
Discussion
Indwelling medical devices are not a clear risk for mortality. Although having at least two indwelling devices was associated with mortality, it is unclear whether increased device usage is a true risk factor or simply a marker of more severe illness. Similarly, CPs were not associated with increased risk of mortality as all patients with CRE had limited treatment options during this time period regardless of the mechanism of resistance.
Table of Contents
Table of Contents
Introduction
Background
Methods
Results
Discussion
References
Tables and Figures
Table 1. Characteristics of patients with carbapenem resistant isolates by those with and without indwelling medical devices
Table 2. Annual case count and incidence of invasive carbapenem resistant Enterobacterales infections, Atlanta, Georgia, 2012 - 2019
Table 3. Characteristics as related to 90-day mortality in patients with invasive carbapenem resistant Enterobacterales infections, Atlanta, Georgia, 2012 - 2019
Table 4. Frequency of devices present in patients with at least two indwelling medical devices in patients with invasive carbapenem resistant Enterobacterales infections, Atlanta, Georgia, 2012 - 2019
Table 5. Risk ratios for 90-day mortality in patients with invasive carbapenem resistant Enterobacterales infections, Atlanta, Georgia, 2012 - 2019
Table 6. Characteristics of patients with carbapenem resistant isolates with available whole genome sequencing, stratified by presence of a carbapenemase gene
Table 7. Type and frequency of carbapenemase genes by organism in patients with carbapenem resistant isolates with available whole genome sequencing
Figure 1. Georgia Emerging Infections Program catchment area
Figure 2. Plasmid with a transmissible genetic element
Figure 3. Directed acyclic graph of relationship between indwelling medical devices and 90-day mortality in patients with invasive carbapenem resistant Enterobacterales infections, Atlanta, Georgia, 2012 – 2019
Figure 4. Directed acyclic graph of relationship between carbapenemase gene positivity and 90-day mortality in patients with carbapenem resistant isolates with available whole genome sequencing
Figure 5. Annual case count and incidence of invasive carbapenem resistant Enterobacterales infections, Atlanta, Georgia, 2012 - 2019
Figure 6. Kaplan Meier survival curve for those with versus those without carbapenemase genes in patients with carbapenem resistant isolates with available whole genome sequencing
About this Master's Thesis
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